4th Global Experts Meeting on Neuropharmacology September 14-16, 2016 San Antonio, USA

Biography:

Nachum Dafny received his MS and PhD degrees from Hadassah Medical School in Jerusalem in 1965 and 1969, respectively followed by post-docs at Caltech, UCLA, and Columbia. He is currently a Professor of Neurobiology at the University of Texas Medical School at Houston.

Abstract:

The prefrontal cortex (PFC) is involved in complex planning, learning, memory, attention and integrates sensory information. It was reported that the PFC is dysfunctional in attention deficit hyperactivity disorder (ADHD). Methylphenidate (MPD), a drug often prescribed for the treatment of ADHD, has potential for abuse and misuse. Most MPD studies were completed in adult subjects; however most users are adolescents. The objective of this study was to investigate the acute and chronic dose response characteristics of MPD on PFC neuronal activity recorded in freely behaving adolescent rats. Four groups of animals were used: saline (control), 0.6, 2.5, and 10 mg/kg MPD. Acute MPD elicited a dose response increase in animals’ locomotor activity. Rechallenge with MPD at experimental day (ED10) when compared to the effect of MPD at ED1 showed no significant differences. When the animals were divided into two groups based on their individual responses to chronic MPD exposure, some animals expressed behavioral tolerance and some expressed behavioral sensitization. Electrophysiologically, a dose response characteristic for acute and chronic MPD exposure was observed. With increasing MPD doses, more PFC units responded by changing their firing rate. Moreover, the neuronal responses to chronic MPD recorded from animals expressing behavioral tolerance were significantly different compared to the neuronal population responses recorded from animals expressing behavioral sensitization. The majority of the PFC units recorded from animals expressing behavioral tolerance responded to MPD predominately by decreasing their firing rates, whereas PFC units recorded from behaviorally sensitized animals mainly showed an increase in their firing rates.

Biography:

The prefrontal cortex (PFC) is involved in complex planning, learning, memory, attention and integrates sensory information. It was reported that the PFC is dysfunctional in attention deficit hyperactivity disorder (ADHD). Methylphenidate (MPD), a drug often prescribed for the treatment of ADHD, has potential for abuse and misuse. Most MPD studies were completed in adult subjects; however most users are adolescents. The objective of this study was to investigate the acute and chronic dose response characteristics of MPD on PFC neuronal activity recorded in freely behaving adolescent rats. Four groups of animals were used: saline (control), 0.6, 2.5, and 10 mg/kg MPD. Acute MPD elicited a dose response increase in animals’ locomotor activity. Rechallenge with MPD at experimental day (ED10) when compared to the effect of MPD at ED1 showed no significant differences. When the animals were divided into two groups based on their individual responses to chronic MPD exposure, some animals expressed behavioral tolerance and some expressed behavioral sensitization. Electrophysiologically, a dose response characteristic for acute and chronic MPD exposure was observed. With increasing MPD doses, more PFC units responded by changing their firing rate. Moreover, the neuronal responses to chronic MPD recorded from animals expressing behavioral tolerance were significantly different compared to the neuronal population responses recorded from animals expressing behavioral sensitization. The majority of the PFC units recorded from animals expressing behavioral tolerance responded to MPD predominately by decreasing their firing rates, whereas PFC units recorded from behaviorally sensitized animals mainly showed an increase in their firing rates.

Abstract:

Nachum Dafny received his MS and PhD degrees from Hadassah Medical School in Jerusalem in 1965 and 1969, respectively followed by post-docs at Caltech, UCLA, and Columbia. He is currently a Professor of Neurobiology at the University of Texas Medical School at Houston.

Biography:

After his undergraduate work in the Birla Institute Pilani, India, Dr. Sharma received his Ph.D. from the University of Connecticut. His research is dedicated to the advancement of the field of membrane guanylate cyclases (MGCs). Discovery of the first membrane guanylate cyclase, ANF-RGC, established cyclic GMP as an intracellular hormonal second messenger. Discovery of others demonstrated that the operational principles of the MGCs transduction mechanisms are complex and unique to each form. Contrary to the other two signaling systems, cyclic AMP and IP3, cyclic GMP pathway dispenses with intermediaries. The hormone binds to an MGC and catalyzes its activity directly. The pathway is multifaceted, its molecular design incorporates multiple regulations: by ATP, Ca2+-sensing subunits and atmospheric carbon dioxide. These diverse effectors confer MGC cellular specificity and multi-switching signaling attributes linked with the physiology of cardiac vasculature, smooth muscle relaxation, blood pressure regulation, cellular growth, sensory transductions, neural plasticity and memory.

Abstract:

This presentation covers the latest state-of-the art developments on the biochemistry and physiology of the Membrane Guanylate Cyclase (MGC) field at the basic molecular, technological and clinical levels. (1) The membrane guanylate cyclase transduction system differs from the three-component design of its predecessor cyclic AMP second messenger system: adenylate cyclase, G-protein and G-protein coupled receptors, in that it consists of a single entity, a membrane-spanning protein that serves as both receptor and signal transducer. Notably, it also differs structurally from its soluble form, which is hetero-dimeric and requires heme for its activity. (2) Upon purification and characterization of the first MGC, several major surprises emerged. The MGC is also a surface receptor of the polypeptide hormone, Atrial Natriuretic Factor (ANF). This feature changes the paradigms of the modes of formation and function of the second messenger in cell signaling. Because ANF is the most hypotensive hormone, it paves new ways to understand its mechanism of action at the most basic level and to develop drugs against irregularities of the cardiac vasculature. Application of the mouse genetics exposes a remarkable 7-amino acid residue encoded motif of ANF-RGC that controls all ANF-modulated blood pressure regulated activity. Furthermore, the ANF-RGC discovery creates the impression that the hormonal signal transduction is its exclusive physiological function. (3) The impression crumbles with the discovery of ROS-GC MGC. ROS-GC expands the family; links it with the physiology of photo-transduction; and transcends a strictly neural function. The ROS-GC subfamily represents a new template of MGC signal transduction system. The novel feature is that in a feedback mechanism it interlocks with the light-induced fall in [Ca2+]i occurring in the outer segments of the rods and cones. (4) In contrast to the ANF-RGC, the ROS-GC is two-component transduction machinery. It employs its sensor components, GCAPs and S100B (a CD-GCAP), to capture [Ca2+]I signals and utilizes ROS-GC as a transducer component. (5) Accordingly, the first ROS-GC-modulated photo-transduction molecular model is proposed. It plays a pivotal role in the discovery and therapeutically diagnosed analysis of the ROS-GC gene-linked dystrophies. (6) An extraordinary feature specific for cone photo-transduction is uncovered where the ROS-GC is a bimodal Ca2+ transduction switch. It turns “OFF” as intracellular [Ca2+] rises above 75 nM, but then turns back “ON” when [Ca2+] exceeds 345 nM. The “OFF” mode is controlled by GCAPs and the “ON” mode by S100B. These modes occur uniquely in the outer segments and their occurrence in synapses of the cones in rodent retinas extends the role of ROS-GC beyond photo-transduction to the signaling processes between the photoreceptor and cone ON-bipolar cells. (7) The finding that another Ca2+-sensor CD-GCAP, Neurocalcin  (NC), is expressed in the Inner Plexiform Layer (IPL) of the retina establishes linkage with signaling by additional neurons. (8) The presence of ROS-GC transduction system in the olfactory bulb and of a variant form of ROS-GC, ONE-GC, in the “necklace ONE-GC” neurons links it with the odorant transduction. Here, four amazing features of the Ca2+-modulated ONE-GC transduction system are disclosed. (i) In addition to ROS-GC1, GCAP1 is also a Ca2+-sensor component of ONE-GC. (ii) Yet, in contrast to the ROS-GC, it modulates ONE-GC catalytic activity only in the higher range of Ca2+, K1/2 of 700 nM. (iii) Instead of inhibiting, it stimulates the guanylate cyclase activity. (iv) The ONE-GC captures odorant signals at its extracellular domain and amplifies them at multiple intracellular domains, incorporating features of both ANF-RGC and ROS-GC transduction systems. (9) The presence of GCAP1- and S100B-modulated ROS-GC1 transduction systems in pinealocytes and of the Ca2+-sensor frequenin-modulated ROS-GC-like in hippocampal layers links the Ca2+-modulated MGC transduction system with “Other than Vision-Linked” Neurons. (10) In a total paradigm change, the dogma is shattered that ANF-RGC, is the specific transducer of ANF alone. It is now known that ANF-RGC also transduces a Ca2+ signal. Ca2+ captured by its sensor NCδ directly activates the catalytic module of ANF-RGC. Accordingly, and impressively, targeted gene-deletion mouse model studies demonstrate that both pathways are linked with blood pressure regulation. Their disruption causes hypertension. Thus the ANF-RGC embodies the combined features of hormone receptor and ROS-GC forms of membrane guanylate cyclases. These studies also broaden classification of the Ca2+ sensors. NCδ, originally classified as a neuronal calcium sensor, serves more widespread functions. (11) With the discovery that the Ca2+-bimodal modulated ROS-GC1 transduction switch occurs in the male gonads, the MGC network extends to the fertility field. Finally, (12) in an extraordinary development photoreceptor ROS-GC via a Ca2+-independent mechanism interlinks its CO2 and the Ca2+-modulated signaling modes. Yet, the Ca2+-modulated modes remain segregated. The domain targeted by CO2 is conserved in the family, thus regulation by CO2 may turn out to be a universal property of the membrane guanylate cyclase family.

Biography:

Clint Makino completed his PhD at Florida State University and postdoctoral studies at Stanford University School of Medicine. He is currently an Associate Professor of Physiology and Biophysics at Boston University School of Medicine. He has published more than 50 journal papers and book chapters and serves on the editorial board of Frontiers in Molecular Neuroscience.

Abstract:

In the first step of vision, retinal rods and cones capture light and generate an electrical response. Upon photoexcitation, the visual pigment activates a G protein coupled cascade that results in hydrolysis of the ROS-GC guanylate cyclase-generated cGMP, closure of cyclic nucleotide gated (CNG) cation channels and membrane hyperpolarization. To control the growth of the response and to speed up the recovery, there is a negative feedback loop based on free [Ca2+]. In darkness, Ca2+ enters the photoreceptor through the CNG channel. Channel closure by induced by light prevents Ca2+ entry, but continued extrusion by an exchanger causes the intracellular [Ca2+] to fall. Guanylate cyclase activating proteins (GCAPs) sense the fall and stimulate the ROS-GC catalytic activity to regenerate cGMP. As cGMP returns to the resting levels present in darkness, CNG channels re-open, Ca2+ enters and cGMP synthesis slows to its basal rate. In the presented pardigm, bicarbonate stimulates the membrane guanylate cyclase independently of Ca2+. But in the presence of GCAPs and low Ca2+, the impact of bicarbonate is greater than the sum of each factor in isolation. This synergism between bicarbonate and GCAPs at low Ca2+ has the physiological effect of boosting the maximal response amplitude, quickening photon response recovery and reducing sensitivity to flashes and to steady light.

Biography:

Teresa Duda received her PhD from A. Mickiewicz University Poznan, Poland. In 1987 she joined Dr. Sharma’s research group at the University of Tennessee, Memphis as a post-doctoral fellow and started her work on membrane guanylate cyclase signal transduction. She is now professor at Salus University in Elkins Park, PA and continues to study various aspects of membrane guanylate cyclase signaling. She has published more than 90 papers in high-input journals and has been serving as an editorial board member of Frontiers in Molecular Neuroscience.

Abstract:

As the eye flicks about a scene, a photoreceptor, rod and cone, sees an alternating pattern of light and dark. This pattern is transduced by the photoreceptor outer segment into electrical signals (a mechanism termed phototransduction), and these signals are processed first by the retina, then by the visual cortex, and finally are decoded as the perceived image. In the phototransduction cascade of rods and cones, the second messenger cyclic GMP is generated by membrane-bound guanylate cyclases (ROS-GCs). In darkness, cyclic GMP opens cyclic nucleotide-gated (CNG) channels and a steady influx of Na+ and Ca2+ enters the outer segment and keeps the photoreceptor depolarized. Photons trigger hydrolysis of cyclic GMP, closing the channels and hyperpolarizing the photoreceptor. The recovery phase occurs when the Na+/Ca2+,K+ exchanger reduces intracellular concentration of Ca2+. Guanylate cyclase-activating proteins (GCAPs) sense this fall and stimulate ROS-GCs to synthesize cyclic GMP at a faster rate, leading to recovery of the photoreceptor dark current. The basic phototransduction components of rods and cones are similar, but important differences render rods more sensitive and cones faster with a larger dynamic range. While rods express ROS-GC1, ROS-GC2, GCAP1, and GCAP2, cones express only ROS-GC1 and GCAP1. We have discovered that cone photoreceptors, but not rods, express another Ca2+ sensor, S100B. This protein stimulates cyclic GMP synthesis as intracellular concentration of Ca2+ increases, and this modulation is specific to ROS-GC1, the only guanylate cyclase expressed in cones. Thus ROS-GC1 functions as a Ca2+-bimodal switch that increases its rate of cyclic GMP synthesis when intracellular Ca2+ rises to higher levels or falls to very low levels. We hypothesize that this bimodal feature serves cone function to better operate during daytime when cones are continuously light adapted and their function is to convey both light increments and decrements. While GCAP unimodal modulation of ROS-GC1 in rods provides negative feedback and is responsible primarily for accelerating response recovery, the GCAP/S100B bimodal feature can provide both negative and positive feedback, accelerating both the recovery and the rising phases.

Biography:

Prof James B. Ames has completed his PhD from University of California, Berkeley Chemistry Department and postdoctoral studies from Stanford University School of Medicine. He is currently a Professor in the Chemistry Department. He has published more than 100 papers in reputed journals and has been serving as an editorial board member of Nature Scientific Reports and Frontiers in Molecular Neuroscience.

Abstract:

GCAP1, a member of the neuronal calcium sensor (NCS) subclass of the calmodulin superfamily, confers Ca2+-sensitive activation of retinal guanylyl cylcase 1 (RetGC1). I will present NMR resonance assignments, residual dipolar coupling (RDC) data, functional analysis, and a structural model of GCAP1 mutant (GCAP1V77E) in the Ca2+-free/Mg2+-bound activator state. NMR chemical shifts and RDC data reveal Ca2+-dependent differences for residues 170-174. An NMR-derived model of GCAP1V77E contains Mg2+ bound at EF2, and looks similar to Ca2+ saturated GCAP1 (RMSD = 2.0 Å). Ca2+-dependent structural differences occur in the fourth EF-hand (EF4) and adjacent helical region (residues 164-174 called the Ca2+-switch helix). Ca2+-induced shortening of the Ca2+-switch helix changes solvent accessibility of T171 and L174 that affects the domain interface. Although the Ca2+-switch helix is not part of the RetGC1 binding site, insertion of an extra Gly residue between S173 and L174 as well as deletion of R172, S173 or L174, all caused a decrease in Ca2+-binding affinity and abolished RetGC1 activation. We conclude that Ca2+-dependent conformational changes in the Ca2+ switch helix are important for activating RetGC1, and provide further support for a Ca2+-myristoyl tug mechanism.

Biography:

Saravanan Kolandaivelu completed his graduate program at All India Institute of Medical Sciences (AIIMS), New Delhi, India. He then joined Dr. John Glomset’s group at Biochemistry, University of Washington as Howard Hughes Medical Institute Fellow and then developed his interest in vision research during his tenure as a senior biochemist with Dr. Visvanathan Ramamurthy at West Virginia University. He was then promoted to the rank of Research Assistant Professor in the department of Ophthalmology at West Virginia University. He currently studies the importance of post-translational lipid modification of proteins and its role in retinal function. He was the recipient of a pediatric ophthalmology grant from Knights Templar Eye Foundation. He was also awarded prestigious young investigator travel awards from NIH and FASEB awards to attend national meetings. He published more than 20 papers in reputed journals. Currently, his laboratory is interested in understanding the molecular mechanism behind the role for protein palmitoylation in photoreceptor function.

Abstract:

Retinal photoreceptor neurons are polarized cells with specialized ciliary extensions called outer segments (OS) needed for vision. Modulation of cGMP in the OS by light is essential for our visual perception. Regulation of cyclic GMP (cGMP) in photoreceptors neurons (rod and cones) is controlled by retinal guanylate cyclase (GC), which produce cGMP. Phosphodiesterase 6 (PDE6) is responsible for hydrolyzing cGMP to GMP upon light activation. Previously, we showed that Aryl hydrocarbon receptor Interacting Protein Like-1 (AIPL1), a protein linked with childhood blindness is needed for rod vision. Our studies show that the loss of AIPL1 in rod cells leads to reduced levels of PDE6 and consequent increase in cGMP that is thought to be the culprit behind rapid death of rod photoreceptor cells. The levels of GC, a cyclase needed for synthesis of cGMP in rods remain unaltered. Similar to rods, AIPL1 is needed for cone-mediated visual response. However, in contrast to rods, cones lacking AIPL1 display severe loss of cone PDE6 and GC. The reduction in enzymes mediating cGMP metabolism is accompanied by reduced levels of cGMP. The link between cGMP levels and rod / cone degeneration remains ambiguous and is currently under investigation.

Biography:

Thomas C. Rich received his B.A.E. and M.Sc. in Aerospace Engineering from the Georgia Institute of Technology in 1988 and 1990, and his Ph.D. in Biomedical Engineering from Vanderbilt University in 1996. He is currently a Professor in the Center for Lung Biology and Department of Pharmacology at the University of South Alabama College of Medicine. His research interests include the development of novel approaches to measure second messenger signals in real time, understanding mechanisms underlying signal specificity, and the roles of intracellular signaling pathways in pulmonary physiology and pathophysiology.

Abstract:

Cyclic nucleotides are ubiquitous second messengers known to differentially regulate many cellular functions over a wide range of timescales. Several lines of evidence suggest that intracellular distributions of cAMP and cGMP are not uniform, and that compartmentalization is largely responsible for signaling specificity within the these signaling pathways. However, real time measurements of cAMP and cGMP signals have been hampered by the low signal-to-noise ratio of fluorescence and FRET probes, as well as the inability to simultaneously measure multiple signals at discrete subcellular localtions within the same cell. In addition, measurements are typically performed in two spatial dimensions (2D), further limiting insight into second messenger signaling systems. Here we present novel hyperspectral imaging approaches that increase signal-to-noise ratios of fluorescence and FRET probes and allow real time, multiplexed measurements of intracellular signaling pathways in three spatial dimensions (3D). We have used hyperspectral approaches to visualize cyclic nucleotide gradients in several cell types, including pulmonary endothelial cells. Interestingly, in endothelial cells gradients primarily form along the apical to basolateral axis. These gradients would not be discerned by traditional imaging approaches. These data suggest that 2D imaging studies of cyclic nucleotide compartmentalization may lead to erroneous conclusions about the existence of second messenger gradients, and that 3D studies are required to assess mechanisms of signaling specificity. Results also demonstrate that novel hyperspectral imaging technologies are powerful tools for measuring biochemical processes in discrete subcellular domains. This work was supported by NIH grants P01HL066299, S10RR027535, and the Abraham Mitchell Cancer Research Fund.

Biography:

Boris Tchernychev received his M.Sc. degree in Biophysics from the Department of Biology of Moscow State University. After completing his PhD in Biochemistry at the Weizmann Institute of Science and his postdoctoral training in the laboratory of B. Furie (Beth Israel Deaconess Medical Center), Boris joined the biotech industry where he spent the last 10 years supporting multiple drug discovery and development programs in different therapeutic areas. At present Boris is a Principal Investigator at Ironwood Pharmaceuticals, where his research is focused on further understanding the secretory and pain inhibitory mechanisms of the FDA-approved drug LINZESS (Guanylate Cyclase-C agonist linaclotide).

Abstract:

Linaclotide is a 14-amino acid, minimally bioavailable peptide agonist of Guanylate Cyclase-C (GC-C) approved for treatment of adult patients with Irritable Bowel Syndrome with Constipation and Chronic Idiopathic Constipation. Linaclotide stimulation of GC-C expressed on the intestinal epithelium initiates signaling pathways resulting in improvement of spontaneous bowel movement and symptoms of abdominal pain. The effect of linaclotide on bowel movements is hypothesized to be a result of increased fluid secretion mediated by elevated intracellular cGMP levels following linaclotide binding to GC-C. Previous studies in enterocytes demonstrate that cGMP activates PKGII, leading to phosphorylation of CFTR and NHE3, both located on the apical membrane of enterocytes. PKGII phosphorylation alters the activity and cellular localization of both transporters and results in increased intraluminal concentrations of Cl-, HCO3- and Na+ ions, generating an electrolyte gradient that drives the passive efflux of water into the lumen, thereby accelerating transit. The effects of linaclotide on abdominal pain are hypothesized to be mediated by extracellular cGMP, which decreases the activity of pain-sensing nerves in nonclinical models. Linaclotide stimulation of rat colonic mucosa induces cGMP efflux from both the apical and the basolateral membrane. Efflux of cGMP from the apical membrane is mediated by Multidrug Resistance Protein 4 (MRP4). Inhibition of MRP4-dependent cGMP efflux by MK571 results in accumulation of intracellular cGMP and increased transepithelial ion current, induced by linaclotide. In summary, these data suggest the presence of a novel, previously unrecognized mechanism that functionally couples the secretory GC-C/cGMP pathway to spatially restricted modulation by apical MRP4.

Biography:

Dr.Elangovan Vellaichamy has completed his M.Phil and PhD (Biochemistry) degree from University of Madras, India, and postdoctoral studies from; 1) Hebrew University of Jerusalem, Isreal, 2) The Celveland Clinc Foundation, Cleveland, Ohio, and 3) Tualne University of Health Sciences, Louisiana, USA. He is presently workig as a Professor, Department of Biochemsitry, University of Madras, Chennai, India. He has published more than 45 papers. His area of research interest is on; 1) Natriurteic Peptides and its Receptro System of the heart, and 2) undertanding the disease mechanisms of hypertension, cardiac hypertrophy and hear failure.

Abstract:

The natriuretic peptides (NPs) family is consists of three important peptides namely atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). ANP and BNP elicits its physiological action by specific binding to Natriureitc Peptide Receptor-A/Guanylyl cyclase-A (NPR-A/GC-A), while CNP binds to Natriureitc Peptide Receptor-B/ Guanylyl cyclase-B (NPR-B/ GC-B). Recent studies have suggested that ANP/NPR-A/GC-A and CNP/NPR-B/GC-B system are present in the heart as a negative regulatory mechanisms to antagonize the cardiac growth response to hypertrophic stimuli. Since NPs has the potential to inhibit cardiac hypertrophic growth via NPR-A/NPR-B receptors, understanding the regulation and expression of NPR-A and –B in the heart during the diseased conditions will help to target specific NPRs subtype to increase the physiological actions of NPs, and thus may be useful as therapy for cardiac hypertrophy and heart failure. In this context, we have studied left ventricular (LV) expression of NPR-A and NPR-B, and the functional activity of these receptors during β-adrenergic receptor (β-AR) activation induced hypertrophic growth in experimental rats. The NPR-A expression was markedly reduced (3.5-fold), while the NPR-B expression was up regulated (4-fold) in Isoproterenol (ISO)-treated heart as compared with controls.. Further, in-vitro membranes assay shows that NPR-A dependent guanylyl cyclase (GC) activity was down-regulated (2-fold), whereas NPR-B dependent GC activity was increased (5-fold) in ISO treated hearts. β –blocker (atenolol) treatment normalized the altered expression of NPR-A and –B proteins. Our results suggests that the chronic β-AR activation differentially regulates NPR-A/GC-A and NPR-B/GC-B in the heart. The signifcance of this finding will be discussed during the presentation.

Biography:

Ana Méndez obtained her PhD from the Autonomous University of Madrid (UAM), Spain, and completed her postdoctoral studies at the Zilkha Neurogenetic Institute, Keck school of Medicine of the University of Southern California. She is currently an Associate Profesor at the University of Barcelona (UB), Spain, where she focuses on studying cell signaling and trafficking pathways in photoreceptor cells of the retina, and their connection to inherited retinal dystrophies.

Abstract:

To gain insight into the organization, assembly and trafficking of the RetGC1/GCAPs complex responsible for cGMP synthesis in rods and cones, as well as its modulation in vivo, we set to identify new interactors of Guanylate Cyclase Activating Protein 1 (GCAP1). Pull-down assays were performed with purified GCAP1 in its Ca2+-bound or Ca2+-free form, from bovine rod outer segment preparations. Bound proteins were identified by liquid chromatography and mass spectrometry (LC-MS/MS). A label-free quantitative proteomic analysis was performed to identify proteins with preferential affinity for one of the GCAP1 conformational forms. Thirty-seven proteins were identified with a fold change >3 for Ca2+-bound over Ca2+-free GCAP1. These proteins included several proteins that could have relevant implications for protein stability, ciliary trafficking and disease. Interestingly, we identified very robustly proteins involved in de novo synthesis of GTP. Co-localization of these enzymes with RetGC1 and GCAP1 was observed at the rod outer segment compartment in bovine retinal sections. Extensive biochemical analysis (size-exclusion chromatography of native tissue, crossed immunoprecipitation and pull-down assays and surface plasmon resonance analysis of the binding kinetics) have further confirmed some of these interactions, which involve direct interactions with RetGC1. Our results unveil an interplay between the RetGC/GCAPs complex responsible for cGMP synthesis and the complex responsible for de novo synthesis of GTP. We speculate that this supraorganization of multienzyme complexes could serve to channel nucleotide metabolism, with an integrated modulation depending on the dark/light physiology of the cell.

Biography:

Ichiro Maruyama is a Professor at the Okinawa Institute of Science and Technology Graduate University (OIST). He received his Ph.D. from The University of Tokyo, Japan. Subsequently he was trained as a post-doctoral fellow in MRC Laboratory of Molecular Biology, Cambridge, UK, where he started to work on the nematode Caenorhabditis elegans with an interest in its nervous system. He then moved to The Scripps Research Institute, La Jolla, California, USA, where he started to study molecular mechanisms underlying activation of cell-surface receptors. At OIST, Ichiro Maruyama continues to work on learning, memory and decision-making in C. elegans as well as on molecular mechanisms of transmembrane signaling mediated by cell-surface receptors.

Abstract:

Survival requires that living organisms continuously monitor environmental and tissue pH. Animals sense acidic pH using ion channels and G-protein-coupled receptors (GPCRs), but monitoring of alkaline pH is not well understood. We report here that in the nematode Caenorhabditis elegans, a transmembrane receptor-type guanylyl cyclase (RGC), GCY-14, of the ASEL gustatory neuron, plays an essential role in the sensing of extracellular alkalinity. Activation of GCY-14 opens a cGMP-gated cation channel encoded by tax-2 and tax-4 genes, resulting in Ca2+ entry into ASEL. Ectopic expression of GCY-14 in other neurons indicates that it accounts for the alkalinity sensing capability. Domain-swapping and site-directed mutagenesis of GCY-14 reveal that GCY-14 functions as a homodimer, in which histidine of the extracellular domains plays a crucial role in alkalinity detection. The Ca2+ entry into the cilia of ASEL induces depolarization of the cilial membrane potential, which in turn activates L-type voltage-gated Ca2+ channels containing an EGL-19  subunit for active propagation of electrical signals in the dendrite. These results argue that in addition to ion channels and GPCRs, RGCs also play a role in pH sensation in neurons.

Biography:

Dr. Frans Vinberg received his M.Sc. and Ph.D. in Biomedical Engineering from Aalto University School of Science in Finland. He is currently a Postdoctoral Fellow at Washington University in St. Louis in Dr. Kefalov’s laboratory. He recently received an NIH/NEI Pathway to Independence K99 award. Dr. Vinberg is interested in understanding the molecular mechanisms that could explain the differences in the physiology of rod and cone photoreceptors mediating our nighttime and daytime vision, respectively. Furthermore, he wants to understand how defects in the function of retinal cells lead to blinding diseases. Specifically, Dr. Vinberg is focused on determining how Ca2+ feedback and regulation mechanisms contribute to the biology and pathobiology of mammalian photoreceptors

Abstract:

Absorption of a photon by visual pigment molecule in the photoreceptor outer segment (OS) triggers a G protein signaling cascade that leads to accelerated rate of cGMP hydrolysis, decline in cGMP concentration and reduced Na+ and Ca2+ influx via cGMP-gated cation channels (CNG channels). However, Ca2+ extrusion from the OS by Na+/Ca2+, K+ exchangers persists, causing photoactivation-induced decrease in Ca2+ concentration. The resulting Ca2+–dependent modulation of cGMP synthesis is critical for the ability of photoreceptors to adapt to background light. Retinal Guanylate Cyclases (RetGC) synthetize cGMP in both rod and cone photoreceptors. The activity of RetGCs is regulated by Guanylate Cyclase Activating Proteins (GCAP) in calcium-dependent manner. As background light intensity increases and Ca2+ concentration decreases, the active EF hand binding sites of GCAPs become occupied by Mg2+ instead Ca2+. These Mg2+-GCAPs activate RetGCs, thus accelerating the synthesis of cGMP. Recent studies have shown that both GCAP1 and GCAP2 are involved in modulating rod phototransduction. However, the distinct contributions of GCAP1 and GCAP2 to the physiology of mammalian cones have not been studied. Here we used electrophysiological recordings from mouse retina to investigate how Ca2+ feedbacks via GCAP1 and GCAP2 regulate cGMP and CNG channel current as well as phototransduction and light adaptation in intact mammalian cones. Our results demonstrate that, unexpectedly, GCAP2 can contribute significantly to the regulation of cGMP concentration and light adaptation in mammalian cones at least in the absence of GCAP1.

Biography:

Venkataraman received his M.S. from Madurai Kamaraj University, India and his PhD for the Indian Institute of Science, India. He is currently an Assistant Professor in the Department of cell Biology, Rowan SOM.  He has published more than 50 papers and book chapters.

Abstract:

Circadian rhythms govern several important physiological processes.  The endogenous body clock, which resides in the suprachiasmatic nucleus, is entrained by several zeitgebers, including light.  Disruption of the endogenous clock or phase results in severe dyshomeostasis as observed during jet lag or in shift workers.  It has been documented that cyclic GMP plays a critical role in setting the phase in circadian rhythms.  However, the molecular mechanism by which it is regulated is unclear.  The results from this study suggest that membrane guanylate cyclase is the likely source in the suprachiasmatic nucleus.  Further evidence is presented that the likely regulator of this activity is the Neuronal Calcium Sensor protein, neurocalcin delta.  It si proposed that the neurocalcin delta/membrane guanylate cyclase system enables a tight coupling to calcium, which is already an established regulator of generation and maintenance of circadian rhythms.

Biography:

Keith Pennypacker has completed his PhD from Penn State University and Post-doctoral studies from National Institute of Environmental Sciences. He is a Professor in the Department of Molecular Pharmacology and Physiology. He has published more than 100 papers in peer-reviewed journals and has been serving as an Editorial Board Member on Translational Stroke Research and Toxicology and Applied Pharmacology.

Abstract:

Many studies have recently demonstrated that the spleen plays a central role in the immune response to stroke, yet few have been successful in describing the precise splenic mechanisms leading to neurodegeneration. Our laboratory was the first to demonstrate that splenectomy decreases infarct volume. Importantly, we have spent the past decade elucidating the inflammatory signals and cell types involved. We have identified the splenic immune cells (monocytes, NK and T) that migrate to the injured hemisphere following experimental stroke. We have also shown that systemic administration of the pro-inflammatory cytokine IFNabolished the protective effects of splenectomy, and administration of IFNγ blocking antibodies reduced injury. Moreover, IFNγ activates and induces expression of IP-10 in microglia. IP-10 attracts IFNγ-expressing T cells to the injured hemisphere and drives a Th1 response while inhibiting the Th2 one. The spleen-derived neurodestructive signaling involves IFNγ associated activation of microglia, which leads to a feed forward signal through IP10 to attract more IFNγ. This leads to the additional expression of IP-10 in M1 microglia to further exacerbate stroke-induced neurodegeneration. This splenic response provides a therapeutic target for novels treatments to reduce stroke-induced neurodegeneration.

Biography:

Georgianna G Gould earned her PhD in Biology in 2001 from Syracuse University, and completed Post-doctoral studies in Pharmacology at The University of Texas Health Science Center at San Antonio (UTHSCSA) under the mentorship of Dr. Alan Frazer in 2007. She was an Assistant Professor of physiology at William Paterson University from 2007-2008. Then she joined the research faculty at UTHSCSA in 2008 to collaborate with Dr. Lyn Daws on novel drug treatments for social behavior impairments in autism. She has published more than 40 peer reviewed articles and book chapters. She involves high school and undergraduate students in her research.

Abstract:

Impaired social interaction is the most prominent and drug treatment-resistant of core autism symptoms. Clinical findings and rodent studies demonstrate serotonin transmission is often disrupted in the socially-deficient brain. For example, dietary or pharmacological depletion of the 5-HT precursor tryptophan (TRP) worsens behavioral symptoms of autism in patients and impairs social interactions in mice, while TRP supplementation improved sociability in some mouse models of autistic symptoms. Also drugs such as buspirone, pargyline and vortioxetine that mimic some postsynaptic effects of serotonin are able to enhance murine social behavior within a limited dose range or time frame. The selective serotonin reuptake inhibitor (SSRIs) Prozac (fluoxetine) enhances sociability in mice. Unfortunately, however, it only does so for limited subpopulations of patients with autism. This could be because SSRI efficacy is diminished if 5-HT transporter (SERT) function is compromised by common and rare gene polymorphisms. Aside from SERT, auxilliary transporters of 5-HT in the brain include organic cation transporters (OCTs) and the plasma membrane monoamine transporter (PMAT) collectively known as “uptake 2”. Uptake 2 transporters remove serotonin from extracellular fluid with greater capacity but lower affinity than SERT. Our hypothesis is that if uptake 2 is blocked, impaired social behavior may improve in a broader population of individuals with autism than presently benefit from SSRI treatments. This hypothesis was tested in two socially impaired mouse models, the BTBR T+tf/J strain and SERT knockout mice. We found that blockade of uptake 2 transporters by systemically-administered pseudoisocyanine decynium-22 promoted social behavior in these mice.

Biography:

Varghese received his PhD from the Department of Medicinal Chemistry, University of Minnesota in 1985. He a postdoctoral fellowship in Professor Josef Fried’s lab in the Department of Chemistry, University of Chicago and a second postdoctoral fellowship in Professor Carl Djerassi’s lab in the Department of Chemistry at Stanford University. He worked with Athena Neurosciences/Elan Pharmaceuticals as a senior member of their Discovery team for 18 years. He then joined the Buck Institute for Research on Aging where he was Director of Alzheimer’s Drug Discovery Network. He started the Drug Discovery Lab at UCLA in 2015.

Abstract:

Alzheimer’s disease (AD) is characterized by the presence of amyloid-β (Aβ ) plaques in brain tissue. Aβ is generated by sequential cleavage of full-length amyloid precursor protein (APP) by β and γ secretase. In an alternative pathway, α secretase cleavage of APP produces the protein fragment sAPPα, known to have trophic effects which support synaptic maintenance and memory. Proteolytic cleavage of APP by the β secretase BACE1 (BACE) as the initial step in production of Aβ has been a major target of AD drug discovery efforts. Overproduction of Aβ results in neuronal cell death and accumulation of amyloid plaques in AD and traumatic brain injury (TBI), and is also associated with stroke due to cerebral amyloid angiopathy (CAA). Others have observed in cells that Aβ production is reduced in the presence of increased sAPPα (Obregon et al, Nat. Commun. 2012). We therefore performed studies to determine the mechanism and revealed for the first time that sAPPα is a potent endogenous direct inhibitor of the BACE enzyme, and that this inhibition is likely by an allosteric mechanism. Furthermore, using small-angle x-ray scattering (SAXS), we show that sAPPβ, which is identical to sAβPPα except for a 16-amino acid truncation at the carboxy terminus, adopts a completely different conformational structure than sAPPα and, importantly, does not inhibit BACE. Our data thus reveal a novel mechanistic role played by sAPPα in regulating overproduction of Aβ and restoring neuronal homeostasis and neuroprotection. Identification of sAPPα as a direct BACE inhibitor would lead to the design of new therapeutics targeting pathologies associated with overproduction of Aβ. In this regard, we have identified through screening a repurposed drug F03 used in the treatment of post-operative nausea and vomiting (PONV) that increases sAPPα in the brain and is currently in a Phase1b/2a clinical trial in Australia in subjects with MCI due to AD. Alzheimer’s disease (AD) is characterized by the presence of amyloid-β (Aβ ) plaques in brain tissue. Aβ is generated by sequential cleavage of full-length amyloid precursor protein (APP) by β and γ secretase. In an alternative pathway, α secretase cleavage of APP produces the protein fragment sAPPα, known to have trophic effects which support synaptic maintenance and memory. Proteolytic cleavage of APP by the β secretase BACE1 (BACE) as the initial step in production of Aβ has been a major target of AD drug discovery efforts. Overproduction of Aβ results in neuronal cell death and accumulation of amyloid plaques in AD and traumatic brain injury (TBI), and is also associated with stroke due to cerebral amyloid angiopathy (CAA). Others have observed in cells that Aβ production is reduced in the presence of increased sAPPα (Obregon et al, Nat. Commun. 2012). We therefore performed studies to determine the mechanism and revealed for the first time that sAPPα is a potent endogenous direct inhibitor of the BACE enzyme, and that this inhibition is likely by an allosteric mechanism. Furthermore, using small-angle x-ray scattering (SAXS), we show that sAPPβ, which is identical to sAβPPα except for a 16-amino acid truncation at the carboxy terminus, adopts a completely different conformational structure than sAPPα and, importantly, does not inhibit BACE. Our data thus reveal a novel mechanistic role played by sAPPα in regulating overproduction of Aβ and restoring neuronal homeostasis and neuroprotection. Identification of sAPPα as a direct BACE inhibitor would lead to the design of new therapeutics targeting pathologies associated with overproduction of Aβ. In this regard, we have identified through screening a repurposed drug F03 used in the treatment of post-operative nausea and vomiting (PONV) that increases sAPPα in the brain and is currently in a Phase1b/2a clinical trial in Australia in subjects with MCI due to AD.

Biography:

Hua Su has received different levels of trainings at the Nanjing Medical University, Xian Jiaotong University and Beijing Medical University. She joined the faculty at University of California, San Francisco in 1996. Currently, she is a Professor and the Associate Director for Basic Science Research at the Center for Cerebrovascular Research, Department of Anesthesia and Perioperative Care. She has published more than 80 papers in reputed journals and has been serving as an Editorial Board Member of many scientific journals.

Abstract:

Stroke is an important risk factor and one of the most devastating complications of bone fracture. We showed previously that bone fracture at the acute stage of ischemic stroke worsens, and activation of 7 nicotinic acetylcholine receptor 7 nAchR) improves stroke recovery through attenuation of inflammation. We hypothesized that activation of 7 nAchR also reduce astrocyte oxidative stress and improves blood-brain barrier integrity. Stroke model was created by permanent occlusion of the distal middle cerebral artery (pMCAO). Tibia fracture was perform 1 day after pMCAO. Mice were treated intra-peritoneally with 0.8 mg/kg PHA 568487 (PHA, 7 nAchR-specific agonist), 6 mg/kg methyllycaconitine (MLA, 7 nAchR antagonist), or saline 1 and 2 days after pMCAO. Brain water content was assessed by measuring the wet and dry weight 3 days after pMCAO. The expression of monoamine oxidase B (MAO-B) in astrocytes and tight junction proteins were quantified. We found tibia fracture increased water content in the ischemic stroke brain (p<0.001) and MAO-B positive astrocytes, and decreased tight junction protein expression. Compared to saline treatment, PHA treatment reduced and MLA increased water content, and MAO-B positive astrocytes in pMCAO and pMCAO plus tibia fracture mice . PHA treatment also increased and MLA decreased tight junction protein expression. Therefore, in addition to inhibiting inflammation, activation of α7 nAchR also reduces astrocyte oxidative stress and improves blood-brain barrier integrity. Thus, the 7 nAchR-specific agonist can be developed into a new therapy for improving recovery of patients with stroke or stroke plus bone fracture.

Biography:

Kailash N. Pandey is a Professor and Vice Chair in the Department of Physiology, Tulane University, School of Medicine. He received M.Sc. from Kanpur University, India, and Ph.D. in 1979 from University of Kentucky, Lexington. He completed postdoctoral at Vanderbilt University and subsequently was promoted to faculty. In 1990, he moved to Medical college of Georgia and in 1997 joined Tulane University, School of Medicine. The research in his laboratory has focused on atrial natriuretic peptide (ANP) and guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA)-mediated regulation of blood pressure and cardiovascular homeostasis. His laboratory deduced the amino acid sequence of murine GC-A/NPRA and genomic sequence of Npr1 (coding for GC-A/NPRA). In collaboration with Professor Oliver Smithies (University of North Carolina), they established genetically altered mouse models with varying Npr1 gene copies numbers (0-, 1-, 2-, 3-, and 4-copy) to conduct molecular physiological studies of hypertension and cardiovascular diseases. He has published 106 research articles, 21 book chapters, 221 abstracts, Special Guest Editorship of the Journal of Peptides, and Editorship of one book. He has trained more than 40 postdoctoral fellows and students and his research has been continuously funded by grants from NIH and AHA and held AHA Established Investigatorship Award. Currently, he is on the editorial board of six Journals and served as the reviewer on several NIH and AHA study sections.

Abstract:

The mechanisms regulating high blood pressure are known to have a strong genetic component; however, the specific genes involved in the pathogenesis of hypertension are not well defined. A key regulators are atrial and brain natriuretic peptides (ANP, BNP), signaling through guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) and the second messenger cGMP. Currently, the mechanisms regulating the transcriptional activation and functional expression of Npr1 (coding for GC-A/NPRA) and receptor signaling are not well understood. To delineate the mechanisms of transcriptional regulation and expression of Npr1 and receptor signaling, we determined the interactive roles of all-trans retinoic acid (ATRA), transcription factors (Ets-1, SP-1), and histone deacetylases (HDACs). Deletional analysis of Npr1 promoter, luciferase assay, and chromatin immunoprecipitation indicated that ATRA dramatically enhanced Npr1 promoter activity in a time- and dose-dependent manner in primary cells in vitro and kidneys of intact animals in vivo. The transcriptional stimulation of Npr1 enhanced the guanylyl cyclase (GC) activity of receptor and the intracellular accumulation of second messenger cGMP; however, subsequently suppressed the expression of proinflammatory and fibrotic genes in the hypertensive haplotype (Npr1+/-) mice. The chromatin immunoprecipitation analysis indicated that the binding of Ets-1 and Sp1 to Npr1 promoter recruited p300 to form a transcriptional co-activation complex and increased the acetylation of histones H3 and H4. In contrast, Npr1 promoter embodying transcription factor delta-crystalline enhancer binding factor-1 (δEF-1) exhibited a repressive effect on Npr1 transcription in response to transforming growth factor-beta 1 (TGF-β1). Our results have provided the evidence that stimulatory molecule ATRA upregulated Npr1 transcription and receptor signaling by recruitment of Sp1, Ets-1, and p300 complex to Npr1 promoter in the disease state. On the contrary, TGF-β1 repressed the Npr1 transcription and receptor signaling, including decrease in GC activity and intracellular accumulation of cGMP and subsequent increase in proinflammatory and fibrotic markers. Our findings are significant for understanding the functional roles of Npr1 and receptor signaling for possible molecular therapeutic targets in the treatment and prevention of hypertension and cardiovascular diseases.

Biography:

Kazue Takayanagi has completed her PhD from Tokushima University, School of Medicine, after completing MD from Kobe University School of Medicine. She was a pediatiric surgeon and changed her career to healthcare administration and then geriatrics. She is the Director of Aoi Royal garden Musashikosugi ,the geriatic Centre from the director of Seiwaenn geriatric Center,since April,2016 and Medical Cooperation Seiwakai, Japan, and also work as a part-time Lecturer of Medical Education Center, Nippon Medical School, Tokyo, Japan. She has published more than 30 papers on laughter and has been serving as a Chairperson of Laughter Academy.

Abstract:

Introduction: The differences in verbal and emotional responses to a baby seal robot, PARO, of elderly people with dementia residing at an elderly nursing care facility were analyzed. There were two groups: one was with mild/moderate dementia (M-group) in the general ward, and the other was with severe dementia (S-group) in the dementia ward. Method: Each elderly resident interacted with either PARO or a control (stuffed lion) brought by a staff at each resident’s private room. Their responses were recorded on video. Behavioral analysis of the initial 6 min of the interaction was conducted using a time sampling method. Results: In both groups, subjects talked more frequently to PARO than to Lion, showed more positive changes in emotional expression with PARO than with Lion, and laughed more frequently with PARO than with Lion. Subjects in M-group even showed more negative emotional expressions with Lion than with PARO. Furthermore, subjects in S-group showed neutral expression more frequently with Lion than with PARO, suggesting more active interaction with PARO. For subjects in M-group, frequencies of touching and stroking, frequencies of talking to staff member, and frequencies of talking initiated by staff member were significantly higher with Lion than with PARO. Conclusion: The elderly people showed greater interest in PARO than in Lion. The results suggest that introducing PARO may increase willingness of the staff members to communicate and work with elderly people with dementia, especially those with mild/moderate dementia who express their demand of communication more than those with severe dementia.

Biography:

Dr. Masaraf Hussain, has completed MBBS from N.S.C.B. Medical College, Jabalpur, India, followed by M.D. in General Medicine from the same institute. He served as Assistant Professor in the Department of Medicine in North Eastern Indira Gandhi Regional institute of Health and Medical Sciences, Shillong ,India. Thereafter he completed postdoctoral studies in Neurology (D.M. Neurology) from Gauhati University, Assam, India. He is currently Assistant Professor Neurology, in NEIGRIHMS, Shillong, India. He has published several papers related to Neuroinfections, epilepsy.

Abstract:

Scrub typhus also known as tsutsugamushi disease is an acute febrile illness caused by Orientia tsutsugamushi. It is seen in terrains of the “tsutsugamushi triangle”. In the state of Meghalaya situated in North –East India , the disease is well known among the local people as “niangsohot” which means organisms associated with chestnut. Central nervous system involvement is a known complication of scrub typhus, and it ranges from meningitis to meningoencephalitis. The name “typhus” itself is derived from the Greek word “typhos”which means stupor. The study carried out revealed fever with headache and altered sensorium , as the most common presentation of Scrub typhus meningoencephalitis. The duration of fever was longer than that of viral and bacterial meningitis. However differentiating it from Tuberculous meningitis is a challenge, even with cerebrospinal fluid analysis. The pathognomic ‘eschar’ helps in early diagnosis of scrub typhus infection. Doxycycline is the drug of choice. However it is bacteriostatic to O.tsutsugamushi ,and does not cross the blood brain barrier beyond 15-30%.Sometimes progressive neurological damage has occurred inspite of treatment with doxycycline, either due to resistance, immune mediated injury or drug interaction. Injectable azithromycin is a good alternative . In the above study as most patients were critically ill, and injectable doxycycline was not available, injectable azithromycin was used along with oral doxycycline. Recovery was seen in 84.61% patients. Recovery was brisk, and signs of improvement was seen within 48 hours of starting specific therapy. Therefore timely initiation of therapy is essential to avoid mortality and morbidity.

Biography:

Yasui-Furukori has completed his PhD at the age of 28 years from University and postdoctoral studies from Hirosaki University School of Medicine. He is associate professor of department of Neuropsychiatry, Hirosaki University. He has published more than 260 papers in reputed journals and has been serving as an editorial board member of repute.

Abstract:

Previous studies have reported changes in the dimensions of the Temperament and Character Inventory (TCI) after patients with major depressive disorder are treated. We aimed to investigate the changes in the TCI dimensions after paroxetine, a SSRI, treatment in patients with major depressive disorder. Forty-eight patients were enrolled in this study and were treated with 10-40 mg/day of paroxetine for 6 weeks. The TCI was completed twice, at weeks 0 and 6. We used the Montgomery-Asberg Depression Rating Scale (MADRS) to evaluate patients. The participants were divided into three groups (responders, non-responders, and early responders) based on treatment response. The scores of each dimension of the TCI were compared before and after treatment using repeated-measures two-way analyses of variance. In the responders group (n = 24), no TCI dimension scores changed significantly during treatment, but the interaction between sex and MADRS score change was significantly associated with the results. In the non-responders group (n = 15), the self-directedness score increased significantly during the treatment period (p = 0.000), and the change in MADRS score significantly affected the results. In the early responders group (n = 9), no TCI dimension scores changed significantly during treatment. The results of the present study may reveal a possible correlation between paroxetine treatment and changes in personality traits.

Biography:

Dr. Burke received his Bachelor of Arts (Psychology) from SUNY Plattsburgh in upstate New York in 1996. He then went on to complete his doctorate at McGill University in Montreal (Biology) and a post-doctoral fellowship in Physiology at the Université de Montréal. In 2010, he joined the Department of Physiology at Howard University as an Assistant Professor. Dr. Burke’s research focuses on neurodevelopment and the effects of developmental intrusions in non-human primates. He is currently funded by the Behavioural Science Foundation (St. Kitts) and the NIH (R03MH107261-01).

Abstract:

Pediatric HIV infection remains a global health crisis with an estimated 650 children under the age of 15 years becoming infected with HIV-1 each day. Only about 25% of the estimated 2.5 million children under the age of 14 living with HIV-1 receive anti-retroviral therapy (ART). Perinatally HIV-1 infected individuals are disproportionately affected by HIV-1 related neurological impairments in comparison to adult infected patients and will often display neurobehavioral deficits prior to significant immunosuppression. Neurocognitive impairment is associated with a greater risk for disease progression and poorer morbidity, even in the advent of ART. As evidenced from the scarcity of neuroimaging and pathological reports, a main and obvious obstacle in pediatric HIV-1 research is sample access, therefore, it is critical to design and test potential intervention therapies in pediatric animal model systems. To this end, the present project takes advantage of ongoing pediatric SIV pathogenesis and vaccine studies to test the hypotheses associated with the neurological consequences of pediatric SIV infection. Perinatal rhesus macaques (Macaca mulatta) received intravenous inoculation with 100 tissue culture infectious doses 50% (TCID50) of SIVmac251 or vehicle (control n=4). Plasma viral loads were quantified by real-time RT-PCR. After a 6-18 week survival time, the animals were sacrificed and the brains prepared for quantitative histopathological analysis. Serial-sections spanning the entire hippocampus were immunostained for SOX-2, glial fibrillary acidic protein (GFAP), nestin, or doublecortin that are putative markers for actively proliferating stem cells, astrocytes and immature neurons respectively. Data from this model indicates that, within two months of infection, SIV significantly reduces the hippocampal neuronal population in the pyramidal layer of the CA1, CA2, and CA3 subregions. There is also a loss of nestin- and doublcortin-positive neurons indicating a reduction in immature neurons along with a reduction in SOX-2 positive cells. The loss of neurogenic capacity may contribute to the rapid and persistent neurocognitive decline associated with pediatric HIV infection. This model presents a platform in which to test therapeutic interventions aimed at ameliorating the negative consequences of HIV-1 in the CNS, specifically targeting the neurogenesis pathway.

Biography:

Takashi Kitajima joined ONO Pharmaceutical Co., LTD. after graduating from University of Shizuoka in 2000. He is a research project leader of ONO-2952 and a head of Group II, Discovery Research Laboratories I.

Abstract:

The translocator protein 18kDa, TSPO is mainly located in the outer mitochondrial membrane of steroid producing cells, including glial cells, and regulates cholesterol transport from intracellular sources into mitochondria, a rate-limiting step in steroidogenesis. Neurosteroids act as allosteric modulators of excitatory and/or inhibitory neurotransmission and its levels are drastically changed by stress. ONO-2952, a novel selective TSPO antagonist inhibited both stress-induced increase in neurosteroid production and noradrenaline release in the brain of stressed rats. ONO-2952 dose-dependently inhibited stress-induced rectal hyperalgesia and defecation with brain TSPO occupancy of more than 50%. In addition, ONO-2952 inhibited conditioned fear stress-induced freezing behavior and cholecystokinin tetrapeptide, CCK-4 induced anxiety behavior with an efficacy equivalent to that of benzodiazepines. It should be noted that ONO-2952, unlike diazepam, did not affect passive avoidance behavior. Furthermore, ONO-2952 inhibited hyperemotionality and anxiogenic-like behavior in olfactory bulbectomized rat. In fibromyalgia models, ONO-2952 inhibited hyperalgesia induced by repeated cold stress or acid saline injection. The present findings indicate that ONO-2952 is a promising candidate for the treatment of stress-related disorders, such as irritable bowel syndrome, depression, anxiety disorders and fibromyalgia.

Biography:

In 2013, Thomas Grund received his Master of Science focussing on the invovlement and regulatory role of extracellular Ca²⁺ on oxytocin-mediated signaling pathways. Currently, he is a PhD student in his last year in the Neumann Lab at the University of Regensburg, Germany, where he investigates how neuropeptides such as oxytocin and neuropeptide S orchestrate fear and anxiety in rodents.

Abstract:

Oxytocin (OXT) and Neuroeptide S (NPS) are known modulators of socio-emotional and neuroendocrine stress reponses. Both neuropeptides were shown to be released within the brain, and their receptors are abundantly expressed in hypothalamic and other limbic brain regions. Both OXT and NPS have been shown to exert robust anxiolytic effects, and we could localize such anxiolytic activity within the PVN (OXT, NPS), the central (OXT) and medial (NPS) amygdala. Anxiolytic effects of chronic OXT and acute NPS could also be found in rat models of pathological hyper-anxiety, such as in rats selectively bred for high anxiety-related behaviour. Moreover, both neuropeptides are involved in extinction of conditioned fear. However, whereas OXT was found to reverse social fear in social fear-conditioned mice, NPS seems to be effective during both social and cued fear extinction. Because of these similar behavioural effects we tested whether OXT mediates the anxiolytic effects of NPS. Indeed, central pretreatment with OXT receptor antagonist blocked NPS-induced anxiolysis in rats. Current studies are focussed on investigating the functional relationship between these neuropeptides in the context of social and cued fear conditioning and generalized anxiety. Despite the increasing knowledge regarding the behavioural effects of OXT and NPS, the receptor-mediated signaling cascades are largely unkown. We could identify several intraneuronal pathways within the PVN linked to OXT or NPS receptors, which include, for example, the MAP kinase pathway, which seems important for the local anxiolytic effects of OXT. Deeper knowledge into the molecular mechanisms of action are needed before neuropeptides can be considered a treatment option for diseases associated with socio-emotional dysfunctions. This research was supported by the Deutsche Forschungsstiftung, EU (FemNat-CD) and BMBF.

Biography:

Ji-Ho Park has completed his PhD from University of Leeds, UK and postdoctoral studies from Sussex University Interdisplinary Research Centre, UK and Mt Sinai School of Medicine NY. He is a Professor of Physiology, at Alternative and Complimentary Medicine devision in Kyung Hee University. He has published more than 35 papers in reputed journals.

Abstract:

Artemisia princeps (AP) is a flowering perennial used as a traditional medicine and dietary supplement across East Asia. We examined the influence of chronic oral AP ethanol extract treatment in ovariectomized rats on the induction of long-term depression in a representative synapse (CA3-CA1) of the hippocampus. To address the neuronal effect, synaptic plasticity was examined in accute hippocampal slice with multielectrode array (MEA) system. Bipolar electrical stimulation was applied to the CA2 stratum radiatum region to stimulate the Schaffer collateral (SC) and commissural pathways. After the conditioning stimulation, field excitatory postsynaptic potentials (fEPSPs) were recorded every 60 sec for another 75 min from 59 microelectrodes spanning the hippocampus. Ovariectomized rats demonstrated lower trabecular mean bone mineral densities than sham, validating the establishment of pathology. Against this background of pathology, AP-treated ovariectomized rats exhibited attenuated LTD in CA1 relative to water-treated controls as measured by increased field excitatory post-synaptic potentials (fEPSP) activation averages over the post-stimulation period. While pathological significance of LTD in ovariectomized rats is conflicting, that AP treatment significantly affected its induction offers justification for further study of its influences on plasticity and its related disorders.

Biography:

Hideo Tsukada received PhD from Shizuoka College of Pharmacy, Japan. He was a visiting researcher in Uppsala University PET Center, Directed by Professor Bengt Langstrom, from 1990 to 91. At present, he is the senior manager of PET Center, Central Research Laboratory, Hamamatsu Photonics, Japan, and conducting PET researches in preclinical to clinical stages. He has published more than 250 papers, being awarded by the Society for Nuclear Medicine (2009), and Japan Molecular Imaging Award (2010). He is serving as the visiting Professor in Hamamatsu University School of Medicine, and University of Shizuoka, School of Pharmaceutical Sciences.

Abstract:

FDG-PET is a well-established technique for quantitative imaging of the regional cerebral metabolic rate of glucose (rCMRglc) in living brain. However, the unexpectedly high uptake of 18F-FDG in ischemia-damaged areas suggested that 18F-FDG was taken up into not only normal tissues but also inflammatory regions with microglial activation, which hampers the accurate diagnose of brain function. To solve this problem, the translational research with 18F-BCPP-EF, a novel PET probe for mitochondrial complex 1 (MC-1) activity was conducted using an animal PET to assess the aging effects on MC-I activity in monkey brain (Macaca mulatta). PET scans using 11C-PIB for A, 11C-DPA-713 for inflammation (TSPO), 18F-FDG for rCMRglc, and 18F-BCPP-EF for MC-1 were performed under conscious states in young and aged animals. When plotted VT of 18F-BCPP-EF against SUVR of 11C-PIB in the cerebral cortical regions, it showed a significant negative correlation between them. Plotting of SUV of 11C-DPA-713 against SUVR of 11C-PIB resulted in a significant positive correlation, suggesting that A deposition-induced inflammatory effects with microglial activation. In contrast, plotting of rCMRglc against SUVR of 11C-PIB did not reach statistically significant level. Furthermore, we recently reported in TauTg mice the negative correlation between the uptake of 11C-PBB3, a PET probe for imaging Tau deposition, and MC-I in hippocampus, and positive correlation between memory function and MC-I activity measured using 18F-BCPP-EF. These results strongly suggested that 18F-BCPP-EF could discriminate the neuronal damaged areas with neuroinflammation, where 18F-FDG could not owing to its high uptake into the activated microglia.

Biography:

Maria Lindau, Licensed Psychologist and PhD, maintains a position as Associate Professor at the Dept. of Psychology, Stockholm University, Sweden. She has about 20 publications, and 15 years of experience as neuropsychologist and researcher at memory clinics at Karolinska and Uppsala university hospitals. She is Bachelor of Arts in History, French and Political Science. Mats Najström is PhD, Licensed Psychologist and Licensed Psychotherapist. He is Head of the Institute for Applied Behaviour Science (ITB) at the Dept. of Psychology, Stockholm University, Sweden.

Abstract:

Neurodegenerative disorders usually show characteristic cognitive profiles, determined by the anatomical dispersion of neuronal loss. Short-term/memory decline is a presenting symptom on Alzheimer’s disease, but atypical early signs also occur. The Wechlser Adult Intelligence Scale (WAIS) may be used to differentiate between normal and sub-normal cognitive performance levels, such as pre-dementia stages, AD and related disorders. According to Meyers et al., (2013), a brief measure consisting of a seven-subtest short form (SF) of the WAIS-IV including Block Design (BD), Similarities (SI), Digit Span (DS), Arithmetic (AR), Information (IN) Coding (CD) and Picture Completion (PC) provides a valid means of measuring cognitive level. In order to validate a short form of WAIS-IV on a Swedish non-clinical sample the aim of the present study was to assess the ability of the seven-subtest SF as well as a reduction of the number of subtests in the SF based on standardized Β-values, to predict the full scale IQ (FSIQ) and its indices. WAIS-IV scaled score data from 98 healthy individuals (19-90 years M=46 years, SD=23 years, females=48, males=50) were analyzed with linear regression, which showed that the seven predictors explained 92.5% of the variance in FSIQ. When reducing the SF-set the four highest Β-values were obtained from the following subtests: CD, Β=0.34 (Processing Speed), SI, Β=0.31 (Verbal Comprehension), BD, Β=0.25 (Perceptual Reasoning), and AR, Β=0.23 (Working memory), which showed to be one subtest from each of the four indices. FSIQ prediction rate of these four subtests was 88.1%. Each of the four subtests correlated significantly on p=<0.01 level with its index. To conclude, FSIQ prediction accuracy for the seven-subtest SF is very high, as well as for the four-subtest model. Since the four-subtest model strongly predicts FSIQ, as well as all its indices, it may be a valid, and timesaving, instrument to assess short-term memory (AR, partly CD) deficits typical for different stages of AD, signs on non-amnestic decline in AD, as well as typical clinical manifestations of frontotemporal degeneration, Parkinson’s disease, Lewy body disease, ischemic brain disorders and cognitive dysfunctions associated with depression. In unclear cases additional testing is necessary. Further analyses will reveal possible influences on the norms of age, genus and education.

Biography:

Dr. Saobo Lei has completed his Ph D from the University of Alberta and postdoctoral studies from the National Institutes of Health. He is a professor in the Department of Biomedical Sciences in the University of North Dakota. His research includes modulation of hippocampal and entorhinal functions by neuromodulators including neurotransmitters and neuropeptides. He has published more than 50 papers in excellent journals and has been serving as an editorial board member of more than 10 reputed journals.

Abstract:

Whereas the entorhinal cortex (EC) receives profuse dopaminergic innervations from the midbrain, the effects of dopamine (DA) on GABAergic interneurons in this brain region have not been determined. We probed the actions of DA on GABAA receptor-mediated synaptic transmission in the EC. Application of DA increased the frequencies not the amplitudes of sIPSCs and mIPSCs recorded from entorhinal principal neurons but slightly reduced the amplitude of the evoked IPSCs. The effects of DA were unexpectedly found to be mediated by α1 adrenoreceptors not by DA receptors. DA endogenously released by application of amphetamine also increased sIPSC frequency. Ca2+ influx via T-type Ca2+ channels was required for DA-induced facilitation of sIPSCs and mIPSCs. DA depolarized and enhanced the firing frequency of action potentials of interneurons. DA-induced depolarization was independent of extracellular Na+ and Ca2+ and did not require the functions of Ih channels and T-type Ca2+ channels. DA-generated currents showed a reversal potential close to the K+ reversal potential and inward rectification suggesting that DA inhibits the inward rectifier K+ channels (Kirs). Our results demonstrate that DA facilitates GABA release by activating α1 adrenoreceptors to inhibit Kirs which further depolarize interneurons resulting in secondary Ca2+ influx via T-type Ca2+ channels.

Biography:

Marina Zueva is a Professor of Pathophysiology. She graduated from the Lomonosov Moscow State University (Physiology of Higher Nervous Activity), received her PhD and BiolSciD from Moscow Helmholtz Research Institute of Eye Diseases. Currently, she is the Head of the Division of Clinical Physiology of Vision at the Moscow Helmholtz Research Institute of Eye Diseases. She is a Member of International Society on Clinical Electrophysiology of Vision (ISCEV), European Association on Vision and Eye Research (EVER), European Society of Retina Specialists (EURETINA). She has published over ten peer-reviewed papers in English (over 80 in Russian) and presented over 60 topics at international conferences.

Abstract:

Healthy functions of the brain and visual system are suggested to be intimately tied to the fractal complexity of the temporal/spatial structure of the environmental visual, auditory and other cues. The simplification of incoming sensory information and alterations of intrinsic neuronal noise may contribute to the simplification of the brain morphology, connectivity and activity in age-related neurodegenerative disorders, such as glaucoma and Alzheimer disease. Preservation of the rich variety of environmental stimuli throughout life is substantiated to be crucial for brain health. In certain conditions, including neurodegeneration and amblyopia, this may demand to create a fractal environment (e.g., the fractal flicker). Numerous studies evidence that the neuroplasticity of adult’s brain may be reactivated by a variety of ways. The strategies of Environmental Enrichment (EE) are well studied now. They include the sensory, motor, perceptual and social EE and likely provide a rewiring of neuronal circuits by the opening of windows of neuroplasticity similar to the developmental plasticity. We should note that the wealth of sensations that we receive during the life may be considered as the most significant aspect of EE for the human brain. In addition to the high art, music and our creative activity, the artificial fractal environmental cues may be useful as a therapeutic strategy and ways of rehabilitation and prevention of neurodegenerative diseases. There are various conditions under which a deficiency of complexity of sensations and images created by the brain may occur that we likely have to consider as a “fractal deprivation."

Biography:

Patrizia LoPresti has received training at major universities, including Penn and the University of Chicago. She has made significant contributions in advancing the field of the cytoskeleton in oligodendrocytes and multiple sclerosis, and more recently her work has contributed to understand cognitive decline as an early event during multiple sclerosis disease.

Abstract:

LoPresti (2015) determined the cognitive abilities of mice with relapsing-remitting experimental autoimmune encephalomyelitis (EAE) treated with and without glatiramer acetate (GA) compared with naïve mice. We found that untreated mice with EAE had a significant rate of decrease in memory function over time compared to naïve mice. In contrast, EAE mice treated with GA had a much lower rate of decrease in memory function. Thus, relapsing-remitting EAE unfavorably influences short-term memory and early GA treatment partially protects against memory loss. Of particular interest, although EAE mice had memory decline over 30 days post immunization, their clinical disease scores improved during that time. These findings highlight for the first time degenerative progressive processes during a remitting disease course. The significance of these findings applies to multiple sclerosis and other dementias. Early in the course of degenerative neurological diseases, specific events occur with unrelenting effects on memory function. Moreover, it also shows that the relapsing-remitting form of multiple sclerosis might have underlying degenerative processes that are ongoing yet undetected. It raises the possibility that looks can be deceiving in the diagnosis of multiple sclerosis. Indeed, both remitting and relapsing disease processes might all be present to various degrees at the onset of this disease. Finally, drug treatments are bound to work on the progressive aspects of this disease when given earlier in the disease process.

Biography:

Yan Xing has completed her MD in 2007 from PekingUnion Medical College Hospital of China. Currently ,She is the director and a associate professor of Department of Neurology, Aviation General Hospital of China Medical University.She has published more than 30 papers in reputed journals and has been serving as several editorial board members of repute.

Abstract:

Objective To observe the clinical and imaging characteristics and the changes of autoimmune antibodies in the serum and cerebrospinal fluid (CSF) of patients with neuromyelitis optica spectrum disorders (NMOSDs). Methods The data of 10 patients with NMOSDs in Aviation General Hospital of China Medical University from January 2011 to June 2014 were collected. The clinical and imaging features were retrospectively reviewed, and NMO⁃IgG in serum and CSF, anti⁃nuclear antibody (ANA), homocysteine (Hcy) and thyroid function were analyzed. Results Cranial and spinal MRI of these patients showed that brain stem was involved in 3 cases, cervical cord in 3 cases, thoracic cord in 6 cases, and cervical⁃thoracic cord in one case. Serum NMO⁃IgG were tested in 8 cases, among whom 3 patients were positive (3/8) and 5 were negative (5/8). ANA was positive in one case (1/3), and thyroglobulin (TG) antibody and thyroid peroxidase (TPO) antibody were positive in 2 cases (2/3). Hypothyroidism occured in 2 cases, hyperthyroidism occured in one case, and Hcy rised in 2 cases. Conclusions NMOSDs frequently occur in young and middle⁃aged women. Patients who were highly suspected with NMOSDs should receive tests of autoimmune antibodies in the serum and CSF, and cranial and spinal MRI examination, in order to make a definite diagnosis and receive appropriate treatment. Retesting the autoimmune antibodies should be done in catabasis, in order to identify the relationship between autoimmune antibodies and NMOSDs.

Biography:

Abstract:

Biography:

Jose F Abisambra completed his PhD and Post-doctoral studies in 2010 and 2013, respectively, at the University of South Florida. He is Principal Investigator in the Tau Research Lab at the University of Kentucky. He published more than 23 papers in reputed journals and serves as Editorial Board Member of the Journal of Alzheimer’s Disease. His work is supported by the National Institutes of Health (NINDS, NIA, NIGMS, NCATS, and NIMHD), the US Department of Defense, and the Alzheimer’s Association.

Abstract:

Tauopathies are a group of more than twenty known debilitating neurodegenerative disorders that affect nearly eight million people in the United States. Currently, there is no cure for tauopathies, and there are temporary and limited benefits to current therapeutic strategies. The endoplasmic reticulum (ER) stress sensor PERK (protein kinase R-like ER kinase) has been identified as a participant in the pathogenesis and progression of tauopathies. However, the mechanism by which the PERK pathway causes neuronal dysfunction is still unknown. In this study, we treated rTg4510 tau transgenic mice at a stage when tau pathology is rampant and cognitive function is impaired with a novel and potent PERK inhibitor. The treatment significantly reduced hyperphosphorylated tau species and led to improvement of neuronal function, as determined with a sensitive and innovative imaging technique called manganese-enhanced magnetic resonance imaging (MEMRI) with quantitative R1 mapping. We also found that PERK inhibition mediated these improvements via a pathway that is independent of eIF2. Our results show a novel mechanism of PERK-mediated tau phosphorylation that potentiates pathogenesis and progression of tau pathology. Future efforts aim to delineate the mechanism ruling the tau-PERK relationship. Finally, this study suggests that PERK is a viable therapeutic target to ameliorate neuronal function in tauopathies.

Biography:

Cristina Vittoria Dieni has completed her PhD at the Department of Physiology of University of Perugia (Italy) and the Post-doctoral studies at the Department of Neurobiology of University of Alabama at Birmingham (USA). She is a Research Associate at the Department of Experimental Medicine of University of Perugia School of Medicine. She has published more than 14 papers in reputed journals and has been serving as an Editorial Board Member of repute.

Abstract:

One hallmark of neural activity in the dentate gyrus (DG) is sparse population coding such that only a few percentage of the principle granule cells (GCs) are activated during sensory stimulation. Sparse activation is evident by the minimal activation of GCs in response to afferent input from the perforant path that is primarily maintained by strong synaptic inhibition provided by local GABAergic interneurons. Within the DG, adult neurogenesis continually produces a small population of immature GCs whit high intrinsic excitability and low levels of inhibition that are predicted to be more responsive to afferent inputs from perforant path than pre-existing mature GCs. It has been suggested that the immature GCs are necessary for generating distinct neural representations of similar contexts process also known as pattern separation. But it is surprising that broadly responsive neurons contribute to the pattern discrimination since in network models the addition of excitable immature GCs degrades rather than improve pattern separation. Yet, it is still unclear how immature GCs contribute to DG network activity and pattern discrimination. Here we show that immature GCs display low excitatory innervation that limits their recruitment by stimulation of the perforant path. Moreover using a statistical model that focuses on excitatory synaptic connectivity we found that immature GCs with low connectivity expand the dynamic range of effective pattern separation during low levels of cortical activity, with a small percentage of immature neurons optimal for expansion. Our results predict that small numbers of excitable but poorly innervated immature GCs can facilitate input-output transformations in the DG by maintaining discrete network representations during low levels of entorhinal cortex activity.

Biography:

I was born in Montevideo, Uruguay. I began Medical School, but I never finished it, because after taking Basic Courses I understood my main interest was on Cell Biology research. I entered in the Biophysics Department of the I.I.B.C.E.¹, where they were doing research in peripheral nerve regeneration, subject that I found very attractive and make me pursue years later a PhD on Cell Biology and Neuroscience. I published several papers dealing with axonal protein synthesis (APS). This controversial issue was really new at that time and we entered in a small group of international researchers that were opposing different point of view about. We got some clues supporting the reality of APS. After we published several publications the APS reality began to growth and to be accepted. I competed for different positions until I got the direction of my own Research Department (Proteins and Nucleic Acids Dept.). I directed several Master and PhD students. I got financial support from National Agencies as well as International Agencies (Japanese International Cooperation Agency (JICA), European Union, Iberoamerican Cooperation Agency (Spain), Organization of American States (OAS), Fogarty-NIH, USA). I co organized the International Institute of Collaborative Cell Biology & Biochemistry (IICCBB) with Dr. Cameron, Rio de Janeiro, Brazil. This School got the Bruce Alberts Award for Excellence in Science Education (ASCB, 2012). I collaborated with Professors of different Universities of USA (Stanford, Virginia, MBL-Woods Hole, SUNY-Buffalo) and Europe (Federico II Naples, MBA, Plymouth, GB, Weizmann Inst. Israel).

Abstract:

The existence of RNA in axons now has been demonstrated after accumulation of abundant experimental evidence hardly to question. Much of the disputes turned now to the origin of these axonal RNAs. The neuronal soma as the source of most axonal RNAs has been demonstrated and is indisputable. However, the surrounding glial cells may be a supplemental source of axonal RNAs, a matter scarcely investigated in the literature. Here, we focus on studies addressing the origin of axonal RNAs and ribosomes and we review the few papers that have demonstrated that glial-to-axon RNA transfer is not only feasible, but likely. We describe this process in both invertebrate axons and vertebrate axons. Court and co-workers conclusively demonstrated that Schwann cell to axon ribosomes transfer exists. Moreover, Glia to axon RNA transfer has been demonstrated in Peripheral axons and from Oligodendroglia to central axons. Recently, mRNA transfer has been demonstrated in a more conclusive way. Regarding this, Ion Torrent massive sequencing of immunoprecipitated Bromo-uridine-mRNAs -Schwann cell synthesized-yielded hundreds of axonal mRNAs i.e., neurofilaments, ankirin, actin, etc. The intercellular transport of mRNA has interesting implications, particularly with respect to the integration of glial and axonal function. This evolving field will certainly impact in the understanding of the cell biology and physiopathology of the axon. Moreover, if axonal protein synthesis can be controlled by the interacting glia, the possibilities for clinical interventions in injury and neurodegeneration are greatly increased.

Biography:

Dr. Xavier Figueroa has completed his PhD from Pontificial Catholic University of Chile and postdoctoral studies from University of Virginia, Cardiovascular Research Center. Currently, he is Associate Professor at Pontificial Catholic University of Chile and is the director of the laboratory of Vascular Biology at the Department of Physiology. He has published more than 30 papers in reputed peer-review journals, several of which have been highly cited. Dr. Figueroa’s Lab combines cellular approaches with studies in intact and in vivo preparations to study the mechanisms involved in the control of microvascular function in peripheral tissues and in the brain.

Abstract:

Brain function depends on the coordination of neuronal activity and cerebral blood flow by a signaling mechanism known as neurovascular coupling. Neurotransmitters released during an increase in synaptic activity (e.g. glutamate) initiate a Ca2+ signaling in astrocytes, which activates the release of vasoactive factors from astrocytic endfeet to parenchymal arterioles. Then, changes in neuronal activity are coupled to local blood flow through regulation of arteriolar diameter. Although NO is one of the most important signaling molecules in vascular physiology, its participation in neurovascular coupling is controversial. However, astrocytes express the Ca2+-dependent NO-synthetizing enzymes eNOS and nNOS and NO modulates the activity of channels formed by connexins (gap junction channels and hemichannels) or pannexins, which coordinate the neurovascular coupling-associated astrocyte signaling. The participation of NO in the neurovascular coupling initated by metabotropic glutamate receptor (mGluR) stimulation was assessed in primary cultures of astrocytes and rat brain slices. NO production, vasomotor response of brain cortex arterioles, activity of connexin hemichannels and pannexin channels, changes in [Ca2+]i and ATP release were evaluated. The results indicate that NO, but unexpectedly, also Ca2+ homeostasis modulator 1 (CALHM1) channels, are essential for the astrocyte signaling that mediates neurovascular coupling. Stimulation of astrocytes mGluRs leads to NO-mediated activation of CALHM1 channels by S-nitrosylation, which evokes ATP release. The subsequent ATP-dependent purinergic receptor stimulation induces the opening of Cx43 hemichannels and Panx-1 channels, which contributes to the astrocytic Ca2+ signaling. These findings may provide clues to the design of new therapeutic strategies for the treatment of neurodegenerative diseases.

Biography:

Anna Puigdellívol-Sánchez was born in 1971 and completed both the PhD (University of Barcelona –UB-) and the Family and Community Medicine Specialization (St Paul’s Hospital, Barcelona) in 2001. She works as Associate Professor (UB) and as M.D. (Terrassa Health Consortium). The nerve regeneration publications (including assessment of dye toxicity) were performed in collaboration with the Karolinska Institute during the predoctoral and postdoctoral stages. The anatomical 3D and quantification techniques were later applied to neuraxial anesthesia, brain connectomics and advanced confocal microscopy, publishing 19 articles in reputed journals and 4 chapters in a Springer Anesthesia reference atlas.

Abstract:

Severe side effects may occur in intrathecal drug delivery systems in cancer patients, where drugs will be diluted in the cerebrospinal fluid, while painful bone contact occurs frequently during punctures. High variability in CSF volumes (CSFv) explains partly the need of different dosages. CSFv and puncture angles may be previously estimated from MRI. Real CSFv values will be close to those obtained from the use of ‘likely’ thresholds, within the range of ‘maximal’ and ‘minimal’ thresholds. ‘Likely’ thresholds: intermediate selection of gray voxels in the borderline zone between roots and CSF. ‘Minimal’ thresholds: selection of cauda equina roots but not adjacent gray voxels. ‘Maximal’ thresholds: threshold is increased until one voxel in the CSF area appears unlabeled and decreased until that voxel was labelled again, selecting the last. Observers made consistent selections with less than 10 minutes of training. Skin-dural sac distances in MRI are close to the distance (d) between the anterior border of the articular process and the external border of the visible soft tissue in lateral lumbosacral Rx. Approximate individualized puncture angle Ì´ inverse cosine [d/ √(1+d²) ] from 1cm paramedian. Significant differences in thresholds exist in the different anatomical area (conus medullaris, upper lumbar levels – cauda equina roots located dorsally within the dural sac- and caudal lumbar levels - roots located laterally-). The estimated range of CSFv within cases is 14%±11%, but maximal/minimal CSFv between cases following a single threshold criterion reached the 210%, suggesting the huge need of individualizing dosages taking the CSFv values into account.

Biography:

Stephanie C Joachim has worked as a post-doc at the Alcon Laboratries in Fort Worth, TX, and the University Eye Clininc in Mainz, Germany, after completing her MD. She is currently head of Experimental Eye Research at the University Eye Clinic at the Ruhr-Unversity Bochum (Germany). She has recieved serval research awards and published more than 40 papers in international journals.

Abstract:

During multiple sclerosis (MS), inflammatory demyelinating lesions develop in the CNS. Patients can experience permanent vision loss after optic neuritis occurs. In an experimental autoimmune encephalomyelitis (EAE) model cell infiltrations (p = 0.0047) and demyelination (p = 0.0018) of EAE nerves strongly correlates with the clinical signs (r> 0.8). In the retina, EAE leads to a significant loss of retinal ganglion cells (RGCs; p< 0.0001). Additionally, an increased apoptosis rate is noted in these retinas (p = 0.0222). EAE also leads to a long lasting activation of microglia (p < 0.05) and a macroglia response in ocular tissues, probably due to the apoptosis of RGCs. Based on our findings, we propose, EAE first starts as an autoimmune disease by causing neuroinflammatory responses against the myelin sheaths. This results in demyelination and inflammation in the optic nerve. In the second phase, it continues as a neurodegenerative disease noticeable by apoptosis of RGCs due to axon demyelination. During the third phase, the apoptosis of RGCs induces to an activation of inflammatory processes in the retina, like IL-6 production and activation of astrocytes and microglia.

Biography:

Enzo Wanke is senior Professor of physiology and has a ResearchGate score of 41.77, 6500 citations in 146 articles, experience in patch-clamp electrophysiology, sodium and potassium channels, neuropharmacology, neural signal processing, neural coding and spike sorting

Abstract:

Study of neurodegenerative disease pharmacology is complicated because investigating drug effects on CNS activity in vivo is time-consuming and expensive. Recent advances in extracellular multi-site recording methods, where signals can be recorded for weeks from functional ex-vivo cortical networks, allows us to test drug effects more directly, and to obtain dose-response data over a longer time-frame. This is important, because normal CNS activity in vivo is disrupted if astrocytes do not sustain their fast [K+]o spatial buffering capacity and ultrafast glutamate uptake processes, but also if microglia are not in a healthy condition. We used neuron/astrocyte/microglial cortical networks to examine the effects of a mild sterile inflammation induced by the bacterial endotoxin lipopolysaccharide (LPS), which significantly modulated neuronal excitability and initiated atypical burst-firing events resembling epileptiform seizures, a recognized feature of various CNS neurodegenerative. We simultaneously analyzed the reverberating bursting activity of a ten thousand neuron network recorded with a multi-electrode array (MEA). This change in excitability was blocked by pre-treatment with various anti-nflammatory drugs and was also sensitive to pM proinflammatory cytokines. Since neuroinflammatory components are involved in a wide range of neurodegenerative, neurological, and psychiatric CNS disorders, we suggest that our methodology might be a useful tool to rapidly screen novel anti-inflammatory/neuroprotectant molecules. The fact that we can detect and analyse long-term effects on neuron activity during microglial activation also opens the possibility to study recently demonstrated roles of “resting” microglia, probably bi-directionally cross-talking with neurons in the developing CNS.

Biography:

Abstract:

Biography:

Dr. Fatih Yakar is graduated from Ankara University Medical School at 2011 and still is a neurosurgery resident in Ibni Sina Hospital at same university. I have three international articles on Pub Med. My subjects of interest are neurovascular surgery, oncology and white matter fiber dissection.

Abstract:

The presence of air in spinal canal is called as “pneumorrhachis.” Nontraumatic, noniatrogenic spontaneous spinal air is an uncommon case. Peripheral alveoli burst due to the increased pressure in alveoli in the case of trauma, asthma, pneumothorax, or pneumomediastinum. Air pass to the mediastinum and then to retropharyngeal space and reaches to epidural space. A 44-year-old female patient was consulted for the waist and leg pain. Neurological examination was intact. The patient had a spinal computed tomography (CT) scan because of claustrophobia. In the spinal CT, the air pack was seen at the level of L5-S1 spinal extradural midline space. It was seen that the air pack in the spinal canal compress the thecal sac anteriorly. The patient has no history of spinal trauma, surgical procedures, medical treatment, asthma, pneumothorax, or pneumomediastinum. The patient was treated with anti-inflammatory drugs and followed without any surgical procedures. Air in the spinal canal was first defined by Gordon and Hardman in 1977. However, spontaneous extradural spinal air is a very rare condition. There are theories related to air entering to the spinal canal have been described. According to Coulier, gas accumulated in degenerated disc reaches to the spinal space by finding a gap from annulus fibrosus. In the absence of neurological deficits, follow-up of the patient with conservative medication is possible.

Biography:

Dr. Oueslati has completed his PhD in 2008 from University of the Mediterranean-Marseilles, France and then he joined the Swiss Federal Institute of Technology in Lausanne (EPFL), Switzerland for a postdoctoral training. In 2015, Dr. Oueslati joined the Department de Molecular Medicine at the Université Laval-School of medicine as assistant Professor. His research program is focused on the study of the implication of alpha-synuclein in Parkinson’s disease pathogenesis and treatments.

Abstract:

Increasing evidences suggest that phosphorylation at S129 (pS129) may be an important regulator of alpha-synuclein aggregation, Lewy bodies formation and neurotoxicity in Parkinson’s Disease (PD) and related synucleinopathies. Recent efforts to probe the relationship between alpha-synuclein phosphorylation and its aggregation and toxicity, using S E/D or SA substitutions, to mimic or to block phosphorylation at this residue, respectively, have yielded controversial results. However, our previous in vitro phosphorylation studies demonstrate that the phosphomimics do not reproduce the structural and functional consequences of pS129 and thus may not be suitable for modeling the effect of phosphorylation in vivo. Recently, we reported that members of the Polo like Kinase family, especially PLK2, phosphorylate α-syn in vitro and in cell culture and in vivo. To validate these findings in vivo and determine whether targeting the PLKs is a viable therapeutic target, we examined the effect of PLK2 overexpression on alpha-synuclein phosphorylation, aggregation and toxicity in a rat model of PD using a recombinant AAV vector-mediated system. The expression and the neuronal localization of each construct were confirmed by immunohistochemistry. The levels of endogenous pS129 were assessed using immunohistochemical and biochemical approaches. The effect of PLK2 overexpression on the dopaminergic neuronal loss was assessed by stereological quantification, and the cellular analysis were correlated with the behavioral effect measured by the cylinder test. This approach allowed us to determine the relationship between alpha-synuclein phosphorylation, aggregation and toxicity and provide novel mechanistic insight into the role of phosphorylation in the pathogenesis of PD and therapeutic strategies based on targeting this modification.

Biography:

Ahmed K Salama is a Professor of Applied Chemistry and Toxicology at Majmaah University, KSA and Alexandria University, Egypt. He has been the head of medical laboratories department from 2007 to2014. He was the Deputy Director of the medical laboratories program at Majmaah University from 2010 to 2014. He obtained his PhD from Duke University Medical Center, North Carolina, USA through a channel system with Alexandria University, Egypt. His overall research interest is directed toward pesticides risk assessment; oxidative stress and tissue damage induced by pesticides; pharmacokinetics and metabolism of pesticides. He has many peer reviewed publications and edited books.

Abstract:

The oxidative damage and pharmacokinetics of pendimethalin were studied in male rat. Rats were divided into four groups. To conduct the pharmacokinetic study, the 1st group received a single oral dose of 109 mg pendimethalin /kg body weight and the 2nd group received a single oral dose of corn oil and served as control. To conduct the oxidative damage study, the 3rd group received four oral doses of 109.4 mg/kg b.wt every other day and the 4th group received corn oil as the same manner and served as control. Rats of 1st and 2nd groups were killed after 0.5, 1, 3, 6, 12, 24, 48, 72, 120, and 168 h. Pendimethalin was readily absorbed and subsequently distributed throughout the body. The peak concentrations of the herbicide reached in serum, liver and kidney at 12 h and in brain at 24 h following administration. The compound began to decline in all tissues as time passed. Pendimethalin disappeared biexponentially from serum, liver, kidneys and brain. The terminal half-life t½ of pendimethalin was 14.0, 15.0, 2.5, and 29.0 h for the serum, liver, brain and kidneys, respectively. At termination of 168 h, the urinary and fecal cumulative excretion rose to 23.81 and 71.21%, respectively. Rats of 3rd and 4th groups were killed 24 h after the last dose. Exposure of rats to pendimethalin caused a significant increase in tissue MDA, LDH and ALP levels as compared to controls. The activities of catalase (CAT) in serum, liver and kidney were significantly increased, while brain CAT activity was significantly decreased due to pendimethalin treatment. Our results indicated that there was no tendency for pendimethalin to retain in rat tissue. The results also showed that pendimethalin exposure had profound influence on the oxidative stress markers and enzyme activities of the exposed male rat and these enzymes can be used as biomarkers in determining pendimethalin toxicity.

Biography:

Abstract:

The Workshop Description

The general goal of the workshop is to make the theory, which we will discuss, a well-known, simple and understandable for people working in various fields of neurosciences and industry.

I want to draw the attention of the experts in various areas of knowledge to the issue of the impact on the brain function of non-linear signals of the environment and the search for opportunities to manage this effects and brain resources.

I would like to trigger a great desire to investigate this area, which is important not only for neuroscience as such, but also for medicine, and to create new, possibly disruptive technologies.

The discussed Issues

In experimental and clinical studies reliable evidence was obtained that sensory, cognitive, physical enrichment of our lives, an increase in the activity of our communication with the outside world, activates brain plasticity. The acquisition of new skills, associated with the re-wiring and establishment of new schemes of neural connections, improves our mental abilities.

However, the search for new technologies to impact on the plasticity of the brain is still relevant and urgently demanded to manage this process better and to create new, more efficient therapeutic strategies.

The theory of “fractality of sensations” establishes the existence of the real relationships (perhaps evolutionarily conditioned) between the complexity of the space-time structure of the environmental signals and the complexity of the neural networks and brain activity that determines the mental health and mental human longevity.

In the workshop, we will outline areas in which a practical application of the tenets of the theory may be found, including:

(i) neuroprotection and recovery of visual neural networks in the pathologies of retinal ganglion cells and their axons;

(ii) rehabilitation of patients with stroke, brain trauma, prevention and attenuation of cognitive decline in the elderly population;

(iii) the new strategy of treatment of neurodegenerative disorders, including Alzheimer's disease and Parkinson's disease;

(iv) increasing the active mental longevity (long-term preservation and enhancement of mental abilities in aging people);

(v) and the restoration and enhancement of cognitive functions in mentally and physically difficult kinds of work in extreme conditions.

To test these hypotheses it is necessary to conduct the research of different design aimed, respectively:

1)  to examine the contribution of artificial visual and auditory stimuli with a strictly ordered (regular) time structure in the weakening and loss of the complexity of the dynamics of the functional activity of the brain;

2) to determine the effectiveness of the non-linear visual and auditory stimulation and effects of other non-linear signals of varying complexity in improving cognitive function and activity of the brain in pathological conditions.

We need to solve the following problems:

•  to reveal the specifics of the development of the retina and brain and neuroplasticity in animals reared in light/dark regime, where light period will consist of flickers at a constant frequency of low-intensity flashes;

•  to examine the specifics of the development of the retina and brain plasticity in animals reared in conditions light/dark, where light period will consist of flickers of very low intensity with a nonlinear fluctuation of the intervals between flashes;

•  to detect features of amblyopia modeling in growing animals on the background of binocular and monocular exposure to low-intensity flashing with an ordered or non-linear time structure compared to animals reared in darkness from birth to adulthood.

• to examine the effectiveness of the use of visual stimuli with non-linear modulated oscillation intervals between flashes of different temporal patterns for prophylactic and therapeutic use in neurodegenerative brain disorders, including Alzheimer's disease and Parkinson's disease;

• to determine the effectiveness of the use of non-linear modulation effects of varying difficulty for preventive and curative purposes in older people with cognitive impairment without neurodegenerative diseases;

• to explore the clinical significance of the use of non-linear modulation effects of varying difficulty for preventive and curative purposes in the pathology of retinal ganglion cells, including glaucoma and diabetic retinopathy;

• to explore the possibility, efficacy and indications for the combined effect of fractal stimulation therapy and white noise;

• to reveal the similarities and differences in the results of the impact of passive music listening, passive exposure to fractal stimuli and white noise to activate the plasticity of physiological and cognitive functions of the brain;

• to estimate significance of the use of non-linear modulation effects for a changing level of internal noise of the retina;

• to identify opportunities and indications for use of the combined effects of nonlinear multimodal therapy;

• to explore the importance of using non-linear modulation effects of varying complexity, including fractal stimulation for preventive and curative purposes in children and adults with amblyopia.

Conclusive remarks:

It is advisable to develop new directions of fundamental and clinical research and technical development, which can:

• Allow to identify patterns of impacts on the brain of nonlinear visual and auditory stimuli of varying complexity, the scope of application of new knowledge and get an ability to manage these effects;

• Enhance the effectiveness of non-linear visual and auditory stimulation, and effects of other nonlinear modulations of varying complexity in improving cognitive function and activity of the brain in pathological conditions.

Knowledge of these laws is necessary for the development of innovative therapeutic strategies for neurodegenerative disorders and amblyopia - diseases of high social importance.

Also, the new knowledge gained in this field of research can help to improve the quality of life of elderly subjects with normal brain function and with cognitive decline, of a long time hospitalized persons, physically challenged people with reduced mobility.

They can contribute to solving some of the problems of urbanization, as well as innovative research capabilities of the brain and related technology solutions in various fields of economy.

For the development of a new priority for the study of the relationship of the fractal complexity of environmental stimuli and brain health is necessary to create the Research and Analytical Centre, "Nonlinear Environment and Resources of the Brain."

Biography:

Miguel A. Morales graduated as MD in 1980, and as MSci and PhD in 1989 at the Universidad Nacional Autónoma de México (UNAM). He made a postdoctoral in McGill University in Montreal, 1989-1992. In 1992 he returned to UNAM where currently he is Full Professor of Neurobiology and Chairman of The Department of Cell Biology & Physiology of the Research Biomedical Institute. Dr. Morales work included the study of synaptic distribution of neurotransmitters involved in co-transmission, and the mechanisms of synaptic plasticity, in the ganglionic long-term potentiation (gLTP); recently he is investigating a possible contribution of neurotrophins in gLTP. He has 42 scientific articles, 7 book chapters and a book. He has graduated 10 students, 5 PhD. Dr. Morales belong to The Society for Neuroscience, Society for Autonomic Neuroscience, International Brain Organization, and currently is President of the Mexican Physiological Society. He has been invited as reviewer in several Journals.

Abstract:

Among their synaptic regulatory actions, neurotrophins (NTs) modulate long term potentiation (LTP). We have shown a differential modulation of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) on sympathetic ganglia LTP (gLTP). BDNF increases gLTP, while NGF produces a concentration-dependent opposite modulation, at 200 ng/ml depresses whereas at 500 ng/ml enhances gLTP. Our work is consistent with the view that gLTP results from an increase in ganglionic synaptic efficacy, and that NTs regulate neuronal excitability. We propose that gLTP enhancement results from the synchronization of a large number of neurons firing phasically, then we postulate that BDNF and NGF 500 increase gLTP by inducing neurons to fire phasically. On the contrary, NGF 200 induces neurons to fire tonically. Herein we studied their contribution of KCNQ/M-currents in setting neuronal activity responsible of neurotrophin-dependent gLTP modulation. We characterized the effects of KCNQ channels agonists and antagonists on gLTP evoked by 40 Hz, 5s stimulation of superior cervical ganglia in vitro. We found that flupirtine, an agonist of Kv7/KCNQ channels, mimicked the stimulatory effects of BDNF and NGF 500 ng/ml on gLTP. While the Kv7/KCNQ channel antagonist XE991 mimicked the decreasing effect of NGF 200 ng/ml, and abolished the stimulatory effect of BDNF and NGF 500 ng/ml. Our data suggest that M-currents contribute to the mechanisms activated by NTs to set the neuronal excitability that underlie gLTP. We propose that gLTP enhancement results from the synchronization of a large number of neurons firing phasically, and that BDNF and NGF 500 ng/ml by activating Kv7 channels reinforce this neuronal firing pattern and thereby increase gLTP. On the contrary, NGF 200 ng/ml by inhibiting these channels induces neurons to fire tonically producing gLTP reduction.

Biography:

Magnus S Magnusson is a Research Professor, and did his PhD in 1983 from University of Copenhagen. He is the creator of the T-system model and algorithms implemented in Theme. Focus on real-time organization of behaviour, co-directed a two-year DNA analysis project, and published numerous papers. He was invited for talks at numerous conferences (including AIMS, IFNA, Neurotalk, Proteomics) and universities in Europe, USA and Japan. He was the Deputy Director in 1983-1988, at the Anthropology Laboratory, Museum of Natural History, Paris. He was repeatedly the invited Professor at Universities of Paris (V,VIII,XIII). Since 1991, he was the Founder and Director of the Human Behaviour Laboratory, University of Iceland. Since 1995, he was in collaboration between 24 universities based on “Magnusson’s analytical model” initiated at the Sorbonne, Paris.

Abstract:

Behavioral analysis has for long been characterized by the use of standard statistical methods developed in other contexts, that is, for quantitative analysis of particular other phenomena or any quantifiable phenomena. Moreover, often due to lack of tools, the counting of behavioural events and states and the measuring of their frequencies and durations has dominated. There has also been some use of multivariate statistics where clouds of points in n-dimensional (data) space reflect relations between behaviours and/or subjects. Hierarchical Cluster Analyses represent such relations in terms of hierarchies of clusters of clusters, however, generally, like with Factor Analysis, the clusters or factors do not describe patterns that recur in time like, for example, repeated words as patterns of letters (phonemes) and repeated phrases as patterns of words or rituals and routines such as greetings and meetings as patterns of simpler behaviours. Standard statistical methods such as sequential analysis are rarely used and typically imply over-simplifying assumptions that may prevent the detection of even abundant repeated patterns. The T-pattern model with its extensions, called the T-system, and corresponding detection algorithms and software, Theme (for Windows), were developed to make such pattern detection feasible and easily available even if computationally intensive. One reason for searching for complex repeated patterns is the possibility of thereby detecting effects of independent variables easily missed by other methods as research increasingly indicates in a number of areas including pharmacology and neuroscience. TPA with Theme allows the analysis of fairly voluminous data, but also of tiny data (just a few events) due to the particular and intensive use of temporal (discrete real-time) information. The T-pattern model with some of its extensions and corresponding algorithms is outlined together with illustrative applications and results.

Biography:

Elzbieta Salinska has completed her PhD 25 years ago from Mossakowski Medical Research Centre, Polish Academy of Scienes in Warsaw. Since then she is a member of Neurochemistry Department and in 2010 became Head of Department. She has published 40 papers in reputed journals. Most of the papers concern studies on experimental models of brain ischemia. Part of the papers concern memory and learning, and are the result of 4 years of collaboration with The Open University, UK. Marcin Gamdzyk and Ewelina Bratek are PhD students supervised by E. Salinska. They both work on the experimental model of birth asphyxia.

Abstract:

Perinatal hypoxia-ischemia is one of the main causes of brain injury in neonates. Hypothermia is the only intervention clinically available and thus the challenge to establish new effective therapies remain a priority in neuroscience. Promising results have been observed using individual treatments of memantine (uncompetitive NMDA receptor antagonist), hyperbaric oxygen (HBO) or mild hypobaric hypoxia (HH) postconditioning. As combination therapies become recently a chance for better results, we decided to investigate whether the combination of memantine (20 mg/kg) treatment with HBO (2.5 ATA) or HH (0.47 ATA) would act synergistically on brain injury evoked by experimental model of birth asphyxia. 7-day old rats were subjected to hypoxia-ischemia (H-I) and then treated either with memantine, HBO, HH or combination of these treatments, started 1h or 6 h after H-I, and repeated for two subsequent days. Application of memantine, HBO or HH resulted in reduction in brain weight deficit, the size of infarct area and apoptosis. Reduction of chosen parameters accompanying oxidative stress was also observed. However, combining memantine with HBO treatment or HH postconditioning resulted in a loss of neuroprotective effects. In conclusion, our results show that memantine, HBO and HH applied separately shortly after H-I do provide neuroprotection, whereas combining memantine with HBO or HH, does not result in additive increase in the neuroprotective effect; on the contrary, combining the treatments increased neurodegeneration. This may suggest that treatments used in our study either compete acting towards the same elements or have the antagonistic effect on the intracellular mechanisms of neuroprotection.

Biography:

Martin Horak has completed his PhD from The 2nd Faculty of Medicine, Charles University in Prague and Postdoctoral studies from the National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, USA. He is currently a Principal Investigator in the Institute of Physiology CAS, an academic non-profit research organization. He has published more than 20 papers in reputed journals and has been serving as an Evaluator of neuroscience and neuropharmacology research grants for the European Commission.

Abstract:

Glutamate is the principal excitatory neurotransmitter in the mammalian Central Nervous System (CNS). The primary ionotropic glutamate receptor subtypes are the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) and N-methyl-D-aspartate receptors (NMDARs), which are present at the postsynaptic membrane of most excitatory synapses in the mammalian CNS. Our research is focused primarily on NMDARs. Nearly every protein that enters the endoplasmic reticulum lumen becomes N-glycosylated, including NMDARs; the glycans are then trimmed and replaced by more complex and variable glycan structures in the Golgi apparatus. However, the identity of the N-glycans that are present on the NMDARs and their role during the early trafficking and functioning of NMDARs have not yet been investigated in detail. Using biochemistry, confocal and electron microscopy, and electrophysiology in conjunction with a lentivirus-based molecular replacement strategy, we found that NMDARs are released from the ER only when two asparagine residues in the GluN1 subunit (N203 and N368) are N-glycosylated. Interestingly, other N-glycosylation sites in the GluN1, GluN2A, and GluN2B subunits do not play a critical role in the trafficking of NMDARs. Furthermore, we found that removing N-glycans from native NMDARs alters the receptor affinity for glutamate. We also revealed 21 lectins that can immunoprecipitate native NMDARs and AMPARs; moreover, two lectins are specific only for NMDARs. Finally, we showed that several lectins alter the functional properties of native NMDARs. Together, our findings suggest that NMDARs contain a specific composition of glycans that can be targeted in the development of novel pharmacological interventions.

Biography:

Sidhartha Tan completed his MBBS from the All India Institute of Medical Sciences, India and is neonatologist and clinician scientist. He is Clinical Professor at Department of Pediatrics, NorthShore University HealthSystem and University of Chicago, IL. He investigates mechanisms of injury that result in cerebral palsy and mental retardation. He has developed an animal model that mimics cerebral palsy, one of the few models of its kind. His research has been continuously funded by NIH since 1992, and is now focused on bringing cures developed in the laboratory to the clinical realm to be used in human mothers and babies.

Abstract:

Cerebral palsy (CP) has significant impact on both patients and society. As there are no curative therapies for CP, stem cells have been proposed as a possible treatment. Human umbilical cord blood cells (HUCBC) containing stem and progenitor cells have been used to treat genetic brain diseases. Previously, HUCBC improved outcomes after hypoxic-ischemic injury in small animals. Clinical trials using HUCBC are underway for neonatal injury and CP. We tested HUCBC therapy in a rabbit model of CP following hypoxic-ischemic (H-I) injury. Following uterine ischemia at 70% gestation, we infused HUCBC in a randomized fashion to newborn rabbit kits after birth with either mild or severe neurobehavioral changes. Infusion of high dose HUCBC, 5x106 cells, dramatically altered the natural history of the injury alleviating the abnormal phenotype including posture, righting reflex, locomotion, tone, and dystonia. Half the high dose showed lesser but still significant improvement. The swimming test however showed that joint function did not restore to naïve control function in either group. Tracing HUCBCs with either MRI biomarkers or PCR for human DNA found little penetration of HUCBC in the newborn brain in the immediate newborn period, suggesting that the beneficial effects were not due to cellular integration or direct proliferative effects but rather to paracrine signaling. In a large animal model, HUCBC improves motor performance in a dose-dependent manner perhaps by improving compensatory repair processes.

Biography:

During his PhD (obtained in 2003 from University Paris Descartes) Nicolas Marie worked on the cellular and molecular mechanisms (signaling, desensitization, receptor trafficking) of human delta opioid receptor regulation in the biochemistry laboratory of University Hospital Center of Caen ( France). Then, he moved to University College Cork (Ireland) as a post-doctoral fellow to work on the mechanisms of intracellular trafficking. In 2005 he joined the team of Dr. Florence as a CNRS scientist to work on preclinical research in drug (mainly cocaine and opiates) addiction using multipte approaches (cell biology, molecular and behavioral pharmacology, biochemistry).

Abstract:

Opiates such as morphine, are the most powerful analgesics however their protracted use is restricted by the development of tolerance to analgesic effects. Previous data suggest that the morphine inability to promote mu opioid receptor (MOPr) endocytosis could be at the origin of the tolerance and the co-injection of morphine with a MOPr internalizing reduces tolerance to morphine. So far, no studies have been conducted to evaluate the ability of methadone to reduce morphine tolerance in morphine-pretreated animals, a treatment sequence that could be encountered in opiate rotation protocol. We investigated the ability of methadone (a MOPr internalizing agonist used in therapeutic) to reverse morphine tolerance and the associated cellular mechanisms in the periaqueductal gray matter, a key region in pain control. Analgesic response was measured following a challenge dose of morphine in the hot plate test and regulation of MOPr (coupling and endocytosis) and some cellular mechanisms involved in tolerance such as adenylate cyclase superactivation and changes in N-methyl-d-aspartate (NMDA) receptor subunits expression and phosphorylation state were investigated. A chronic treatment with morphine promoted tolerance to its analgesic effects and was associated with a absence of MOPr endocytosis, adenylate cyclase overshoot, NR2A and NR2B down-regulation and NR1 phosphorylation. We found that a methadone treatment in morphine-treated mice reversed morphine tolerance to analgesia by promoting MOPr endocytosis and blocking cellular mechanisms of tolerance. Our data might lead to rational strategies to tackle opiate tolerance in the frame of opiate rotation.

Biography:

Hideo Tsukada received PhD from Shizuoka College of Pharmacy, Japan. He was a visiting researcher in Uppsala University PET Center, directed by Professor Bengt Langstrom, from 1990 to 91. At present, he is the senior manager of PET Center, Central Research Laboratory, Hamamatsu Photonics, Japan, and conducting PET researches in preclinical to clinical stages. He has published more than 250 papers, being awarded by the Society for Nuclear Medicine (2009), and Japan Molecular Imaging Award (2010). He is serving as the visiting Professor in Hamamatsu University School of Medicine, and University of Shizuoka, School of Pharmaceutical Sciences.

Abstract:

FDG-PET is a well-established technique for quantitative imaging of the regional cerebral metabolic rate of glucose (rCMRglc) in living brain. However, 18F-FDG is taken up into not only normal tissues but also inflammatory regions with microglial activation, which humpers the accurate diagnose of brain function. To solve this problem, the translational research with 18F-BCPP-EF, a novel PET probe for mitochondrial complex 1 (MC-1) activity was conducted using an animal PET in ischemic brains of Cynomolgus monkeys. Focal ischemia was induced by the right middle cerebral artery occlusion for 3 hr, then PET scans were conducted 7 days post ischemic insult with 15O-gases for regional cerebral blood flow (rCBF) and regional cerebral metabolic rate of oxygen (rCMRO2), and 18F-BCPP-EF for MC-1, 11C-PBR28 for inflammation (TSPO), and 18F-FDG for rCMRglc. The total distribution volume (VT) values of 18F-BCPP-EF demonstrated the significant reduction of MC-1 activity in the damaged area at Day-7. The VT values of 18F-BCPP-EF provided better correlation with rCMRO2 than rCBF. In the inflammatory regions of the ischemic hemisphere detected with 11C-PBR28, higher 18F-FDG uptake and lower VT of 18F-BCPP-EF, and rCMRO2 than those in normal contralateral hemisphere were observed. Furthermore, the neuroprotective effect of FK506-liposome was detected by 18F-BCPP-EF, as improved MC-I activity, in ischemic-damaged regions. These results strongly suggested that the PET scan using 18F-BCPP-EF could non-invasively diagnose the extent of the brain damage and evaluate the neuroprotective effects without any disturbances by neuroinflammation, where 18F-FDG could not, owing to its high uptake into the activated microglia.

Biography:

Dr. Annett Kunkel has completed her PhD in 1999 at the Humboldt-University in Berlin, Germany in the field of motor recovery in chronic stroke patients (Constraint-induced movement therapy). From 1999 to 2001 she completed a secondary education as Clinical Neuropsychologist. Since this time she works up to three years in the neurological rehabilitation and since 15 years in the area of acute neurology. During this time she began her research in patients with Multiple Sclerosis. For almost 5 years she is the leading Neuropsychologist in two neurological partner hospitals (Dept. of Neurology Asklepios Fachklinik Teupitz/Lübben).

Abstract:

Background/Objective: Fatigue, cognitive and affective disorders are relevant symptoms in Multiple Sclerosis (MS). The treatment with natalizumab has a positive effect on physical disabilities in patients with RRMS. Some studies describe improvements in cognition and fatigue over one year of treatment. Only little is known about longer treatment effects especially on fatigue, but also on cognition and mood. Therefore the present prospective open label observational study investigates the effect of natalizumab on fatigue, attention and depression over a treatment period of two years. Methods: 52 patients with RRMS (male=11, female=41; mean age: 33.9+9.1 years) underwent a comprehensive neuropsychological assessment, consisting on different tests of attention (TAP: alertness, divided attention, flexibility, SDMT, PASAT), fatigue (WEIMUS, FSMC) and depression (ADS-L). The assessments occurred immediately before the first administration of natalizumab, after one and two years of treatment. Results: Significant improvements were found in aspects of attention and depression from baseline to follow-up 1 (alertness: reaction time (RT) cued, p=0.02; divided attention: visual RT, p=0.02; SDMT: p=0.02; ADS-L: p=0.047) and from baseline to follow-up 2 (divided attention: visual RT: p=0.000; errors, p=0.01, omissions, p=0.05; flexibility: RT, p=0.05; SDMT: p=0.01; ADS-L: p=0.02). Up to know no significant changes were detected in fatigue probably because of the small sample size especially in the second year of treatment (WEIMUS: N=19, FSMC: N=7). Conclusion: The results show a positive effect of natalizumab on attention in patients with RRMS and for the first time also in depression after two years of observation and support the efficacy of the treatment over two years. More research is needed for fatigue.

Biography:

Jin-Song Bian is an Associate Professor in Department of Pharmacology, Yong Loo Ling School of Medicine, National University of Singapore, Singapore. He earned his PhD degree from the University of Hong Kong. At Albert Einstein College of Medicine in USA, he completed his Post-doctoral training with an American Heart Association fellowship in 2003. His main research interest is biology of endogenous mediators (e.g. hydrogen sulfide). He has published over 80 papers in international journals including Cir Res, ARS, JASN.

Abstract:

Addiction to opioid drugs is a serious clinical and social problem. Withdrawal-induced symptoms are the main cause of keeping drug-dependent individuals craving for continued opioids. Hydrogen sulfide (H2S) is a novel endogenous neuromodulator. The role of H2S in opioid induced syndrome was investigated in the present study. We found that exogenous application of NaHS, an H2S donor, significantly alleviated naloxone-precipitation induced robust withdrawal jumping in mice. Application of NaHS or stimulation of endogenous H2S production suppressed naloxone precipitation induced cAMP rebound and CREB phosphorylation. Our data suggest that H2S may produce beneficial effects against opioid addiction by suppression of AC/cAMP /CREB pathway. Hyperalgesia often occurs in opioid-induced withdrawal syndrome. In the present study, we also studied the effect of H2S on opioid withdrawal induced hyperalgesia. We found that application of NaHS together with three hourly injections of DAMGO (a μ-opioid receptor agonist) attenuated naloxoneprecipitated withdrawal hyperalgesia. RT-PCR and Western blot analysis showed that NaHS significantly reversed the gene and protein expression of up-regulated spinal calcitonin gene-related peptide (CGRP) in naloxone-treated animals. NaHS also inhibited naloxone-induced cAMP rebound and cAMP response element-binding protein (CREB) phosphorylation in rat spinal cord. In addition, NaHS pre-treatment suppressed naloxone-stimulated activation of protein kinase C (PKC) α, Raf-1, and extracellular signal-regulated kinase (ERK) 1/2 in rat spinal cord. In conclusion, our data suggest that H2S prevents the development of opioid withdrawal induced symptoms via suppression of synthesis of CGRP through inhibition of AC/cAMP and PKC/Raf-1/ERK pathways.

Biography:

Nasim Vousooghi became Pharm. D. At the age of 26 and completed her PhD of pharmacology at the age of 33 years from Shahid Beheshti University of Medical Sciences. She is working as assistant profesor and director of research deputy in the departement of neuroscience and addiction studies in Tehran University of Medical Sciences from 2010 till now. She is also the head of genetics laboratory of the Iranian National Center for addiction studies (INCAS). She has published more than 20 papers in prestigious journals.

Abstract:

Genetic and environmental factors are involved in opioid addiction. It is claimed that offspring of addicted people are more prone for drug addiction including opioids. However, the exact mechanisms involved in trans-generational effects of opioids are not much understood. Here we have studied the effects of parental opioid addiction on morphine preference and mRNA expression of dopamine receptors in F1 male offspring. Adult male and female Wistar rats received chronic morphine followed by two weeks drug free period before mating. Two-bottle- choice paradigm was used to measure morphine preference in offspring. The mRNA expression of dopamine receptors was evaluated in prefrontal cortex, nucleus accumbens, hippocampus, and striatum of F1 male animals by Real-Time PCR approach. The results showed that F1male offspring of morphine-exposed parents had higher preference for morphine consumption in comparison to offspring of saline-exposed parents. D1 and D5 dopamine receptors were significantly up-regulated in prefrontal cortex and nucleus accumbens of F1 male offspring of morphine-exposed parents. D5 and D2 receptors were, however, down-regulated in hippocampus. D4 dopamine receptor was up-regulated in hippocampus and striatum and down-regulated in prefrontal cortex. It is concluded that chronic morphine exposure of adult male and female rats before gestation leads to higher morphine preference in their F1male offspring. Furthermore, alterations in the expression of dopamine receptors in the reward pathway could be involved in observed changes in F1 offspring.

Biography:

Ai-Ling Lin completed her PhD and Postdoctoral training as a medical physicist from the University of Texas Health Science Center at San Antonio. She is an Assistant Professor in the Sanders-Brown Center on Aging and Department of Pharmacology and Nutritional Sciences of the University of Kentucky. She has developed and applied multi-metric neuroimaging methods (MRI, MRS and PET) to identify effects of caloric restriction and rapamycin on cognitive aging and Alzheimer’s disease with various animal models. She has published more than 30 papers in reputed journals and continuously received funding from NIH.

Abstract:

Apolipoprotein E ε4 allele (APOE4) is strongest genetic risk facot for late-onset Alzheimer's disease (AD). Brain vascular and metabolic deficits can occur in cognitively normal APOE4 carriers decades before the onset of AD. The goal of this study was to determine whether early intervention using rapamycin could restore neurovascular and neurometabolic functions, and thus impede pathological progression of AD-like symptoms in pre-symptomatic APOE4 transgenic mice. Using in vivo, multimodal neuroimaging, we found that APOE4 mice treated with rapamycin had restored cerebral blood flow, blood-brain barrier integrity and glucose metabolism, compared to age- and gender-matched wild-type controls. The preserved vasculature and metabolism were associated with amelioration of incipient learning deficits. We also found that rapamycin restored the levels of the proinflammatory cyclophilin A in vasculature, which may contribute to the preservation of cerebrovascular function in the APOE4 transgenics. Our results show that rapamycin improves functional outcomes in this mouse model and may have potential as an effective intervention to block progression of vascular, metabolic and early cognitive deficits in human APOE4 carriers. As rapamycin is FDA-approved and neuroimaging is readily used in humans, the results of the present study may provide the basis for future AD intervention studies in human subjects.

Biography:

Tanja Maritzen completed her PhD in the lab of Prof. Dr. Dr. Thomas Jentsch at the Center for Molecular Neurobiology in Hamburg, Germany, after studying molecular biology and biochemistry. Afterwards she joined Prof. Volker Haucke at the Freie Universität Berlin as Post-doctoral fellow. Since 2013, she heads a junior research group at the Leibniz-Institute for Molecular Pharmacology. Her research focuses on the mechanisms underlying synaptic vesicle recycling.

Abstract:

Neurotransmission depends on the fusion of neurotransmitter-loaded synaptic vesicles (SVs) with the presynaptic membrane, which is driven by complex formation between the vesicular SNARE Synaptobrevin2 (Syb2) and target SNARE proteins. SV fusion is followed by endocytic SV retrieval and the reformation of SVs of correct size and composition. With 70 copies per SV Syb2 is the most abundant SV protein, yet, 1-3 Syb2 molecules were reported to be sufficient for basal exocytosis. However, we found that a moderate use-dependent reduction of vesicular Syb2 levels caused by absence of its endocytic adaptor AP180 in vivo impairs neurotransmission leading to excitatory/inhibitory imbalance, epileptic seizures, and premature death. Further reduction of Syb2 levels in AP180-/-/Syb2+/- mice results in perinatal lethality, whereas Syb2+/- mice partially phenocopy loss of AP180. Thus, a large vesicular Syb2 pool maintained by AP180 is crucial to sustain efficient neurotransmission.

Biography:

Jean-Pierre Mothet is Director of Research at CNRS (France). He graduated from the University Pierre and Marie Curie, Paris, in 1996 working with Dr. Ladislav Tauc. Then, he pursued Post-doctoral research with Pr Solomon H. Snyder at The Johns Hopkins School of Medicine (USA). There he elucidated the functions and the synthesis pathway of brain D-serine. In 1999, he moved to the laboratory of Pr Jacopo Meldolesi (Italy) to study exocytosis of neurotransmitters. His team “Gliotransmission and Synaptopathies” investigates the regulation of NMDA receptors at synapses and circuits underlying memory formation in the context of healthy and pathological neuron-glia interactions. He also explores the mechanisms underlying gliotransmission, the process by which glia releases chemical messengers, and the functional relevance for neuronal network dynamics. He serves at the Editorial board Member of Frontiers in Synaptic Neuroscience and PlosONE and he is a member of the ESN council.

Abstract:

The N-Methyl D-Aspartic acid (NMDA) receptors (NMDARs) are key glutamate-gated ionotropic receptors that are central for synaptic plasticity across lifespan but also engaged in the pathogenesis of many brain diseases that affect our societies. For this reasons NMDARs are prime targets for drug development. Activation of NMDARs always requires the binding of a co-agonist that has long been thought to be glycine. However, intense research over the last two decades has have shown that D-serine, an atypical amino acid metabolized by brain cells is the preferential co-agonist for a large proportion of synaptic NMDARs in many areas of the adult brain. Nowadays, a totally new picture of glutamatergic synapses at work is emerging where both glycine and D-serine are involved in a complex orchestration of NMDAR functions in the CNS following temporal and spatial constraints. During my lecture, I will highlight the particular role of each co-agonist in modulating NMDAR at developing and mature central synapses of different brain regions and show how the functions of D-serine and glycine at NMDARs can be pressured by specific neuromodulatory systems. Then, I will show how the discovery of D-serine metabolism and functions have opened new avenues for the development of new drug-based therapies of cognitive deficits during normal aging, for those associated to psychiatric disorders such as schizophrenia but also to prevent cellular damages associated to NMDARs overactivation as observed in early phases of Alzheimer’s disease.

Biography:

Abstract:

Microglia are highly reactive to tissue injury. In response to focal damage, microglia extend their processes toward the compromised tissue. The cell motility aspects of this behaviour have been characterized, but the intracellular events, particularly the Ca2+ responses, have not been systematically studied in microglia due to technical difficulty. Here, we used live two-photon imaging in the PC::G5-tdT reporter mouse expressing the genetically encoded Ca2+ indicator GCaMP5G and fluorescent marker tdTomato in cortical microglia. We found that spontaneous Ca2+ transients in microglial somas and processes were generally low (only 4% of all microglia showing transients within 20 min), but baseline activity was markedly increased when the animals were subcutaneously injected with LPS 12 h before imaging. When challenged with focal laser injury, an additional surge in Ca2+ activity (up to 67%) was observed in the somas and protruding processes, particularly in close proximity to the damaged tissue. Notably, coherent and simultaneous Ca2+ rises in multiple microglial cells were occasionally detected in LPS and bicuculline-treated animals. We have demonstrated that Ca2+ transients were predominantly mediated via purinergic receptors. We also compared the speed of process extension in BAPTA-AM and the purinergic receptor antagonist PPADS-treated animals and showed that BAPTA-AM significantly slowed the process protrusion, but PPADS did not. This study illustrates the suitability of the PC::G5-tdT mouse reporter for investigations of microglial physiology.

Biography:

Al Aditya Khan is a consultant forensic psychiatrist employed by Oxleas NHS (National Health Service) Foundation Trust. He qualified as a doctor in 2002. He has been a member of the Royal College of Psychiatrists, UK since 2007 and completed his specialist training in 2011. Up to 2015 he worked in prison and court services in Kent and London. He currently works in a medium secure hospital the Bracton Centre, Kent, UK. He has published a number of research papers and has presented in various national and international conferences including in Germany, Hungary and Mexico.

Abstract:

Background: The current guidelines dictate that clozapine should be stopped following the emergence of neutropenia. Various alternative approaches have been tried in the past, among them one rarely used alternative being to continue treatment with clozapine with co-prescription of granulocyte colony-stimulating factor (G-CSF). Aim & Method: In this case series, we aim to describe the treatment and progress of a number of patients in a secure psychiatric hospital in the UK. These patients were restarted on clozapine in combination with G-CSF, in spite of previous neutropenia associated with clozapine treatment. Discussion & Conclusion: We hope that this case series will raise the profile of a potentially effective alternative to discontinuing clozapine after neutropenia.

Biography:

Hanna Christiansen has completed her PhD in 2009 at the Philipps University Marburg. After working as an Assistant Professor at different universities, she has received her Full Professorship in 2013 also at the Philipps University Marburg, Department of Clinical Child and Adolescent Psychology. She is the Director of the Department of the Psychotherapeutic Outpatient Clinic and Training Clinic for Children and Adolescents. She has published more than 40 papers in reputed journals and has been serving as an Editorial Board Member of Plos One and Frontiers in Psychology.

Abstract:

Introduction & Objectives: Behavior therapy is a treatment alternative for children with ADHD, and Neuro-Feedback (NF) is a specific one that combines behavioral and neurocognitive elements with good effects, and supposedly without side effects. To date, there is no study on ADHD treatment with NF in a naturalistic outpatient setting. Methods: Based on a power-analysis, a total of 92 children aged 7-11 will be randomized to either NF or Self-Management treatment (SM), stratified for gender and stimulant medication. Children will recieve 36 high-frequent training sessions in 12 weeks with 6 sessions reserved for comorbid problems. Post treatment assessments are scheduled after 36 treatment sessions, as well as 6 and 12 months after treatment termination. Primary endpoints are the Conners 3rd rating scales for parents and teachers, and the Quantified Behavior Test (Qb-Test) that objectively assesses the three ADHD core symptoms inattention, hyperactivity and impulsivity. Results: So far, N=42 children (n=20 NF, n=22 SM) participated in the study with data available. After 36 treatment sessions, children in both groups showed significant and overall large improvements on all Conners parent rating scales and on the majority of teacher rating scales, including academic achievement. Large and significant improvements were also obtained on Qb-test variables. Analysis of 6 months follow-up data demonstrates stability of effects over time. There are no significant differences between groups, yet. Treatment and assessment continues and results from a larger data base will be presented. Discussion: Behavioral treatment in a high frequent naturalistic outpatient setting seems to be very effective in reducing ADHD symptoms, but possible long-term effects and group differences still need to be established.

Biography:

Sang Hyung Lee has completed his PhD from Seoul National University and postdoctoral studies from Seoul National University College of Medicine. He is a professor of the neurosurgery department in SMG-SNU Boramae hospital and the director of cooperation in the same hospital. He has published more than 90 papers in reputed journals.

Abstract:

Cerebral hyperperfusion syndrome (CHS) is a serious complication after carotid endarterectomy (CEA). However, the prevalence of CHS has decreased as techniques have improved. This study evaluates the role of strict blood pressure (BP) control for the prevention of CHS. All 18 patients who received CEA from February 2009 through November 2012 were retrospectively reviewed. All patients were routinely managed in an intensive care unit by a same protocol. The cerebral perfusion state was evaluated on the basis of the regional cerebral blood flow (rCBF) study by perfusion computed tomography (pCT) and mean velocity by transcranial doppler (TCD). BP was strictly controlled (<140/90 mm Hg) for 7 days. When either post-CEA hyperperfusion (>100% increase in the rCBF by pCT or in the mean velocity by TCD compared with preoperative values) or CHS was detected, BP was maintained below 120/80 mm Hg. TCD and pCT data on the patients were analyzed. Ipsilateral rCBF was significantly increased after CEA in the pCT (p=0.049). Post-CEA hyperperfusion was observed in 3 patients (18.7%) in the pCT and 2 patients (12.5%) in the TCD study. No patients developed clinical CHS for one month after CEA. Furthermore, no patients developed additional neurological deficits related to postoperative cerebrovascular complications. Intensive care with strict BP control (<140/90 mm Hg) achieved a low prevalence of post-CEA hyperperfusion and prevented CHS. This study suggests that intensive care with strict BP control can prevent the prevalence of post-CEA CHS.

Biography:

Roberto Federico Villa graduated in Biological Sciences (DSc) and in Medicine and Surgery (MD); he is Associate Professor of Pharmacology at University of Pavia. His research activities on the cerebral energy metabolism evaluated by the functional proteomics and metabolomics are about the physiopathology and pharmacology of the central nervous system in experimental conditions of hypoxia, ischemia, hyperammoniemia, hypoglycemia; molecular mechanisms of aging and drugs' interference; the study of Parkinson’s disease and drugs' actions in dementia; clinical studies on molecular medicine and human genetics on patients affected by dementias and ischaemia. He has published 349 total papers (IF about 350) and has been officially invited to 214 congress since 1993.

Abstract:

Human neuroimaging studies have shown brain energy metabolism abnormalities in mood disorders, indicating the normalization of tissutal bioenergetics after anti-depressants’ (ADs) treatment. However, several experimental studies suggest that antidepressants are inhibitors of mitochondrial function, while others indicate positive effects. In this study, the effects of 21-day treatment with the tricyclic antidepressant Desipramine (15 mg/kg, i.p.) were evaluated on energy metabolism of rat frontal cerebral cortex. Because of brain mitochondria micro-heterogeneity, (a) non-synaptic mitochondria in vivo located in neuronal perikaryon and (b) two types of intra-synaptic mitochondria in vivo located in synapses (“light” and “heavy”) were used. The following enzyme activities have been assayed: citrate synthase (CS), succinate dehydrogenase (SDH), malate dehydrogenase (MDH) for Krebs’ cycle; NADH-cytochrome c reductase (CCR), cytochrome oxidase (COX) for Electron Transport Chain; glutamate dehydrogenase (GlDH), glutamate-oxaloacetate transaminase (GOT), glutamate-pyruvate transaminase (GPT) for glutamate and related amino acids metabolism. In controls, energy-linked enzyme activities are differently expressed in the considered mitochondria, whose metabolic individuality is reflected by enzyme kinetics, as previously shown in physiological aging, experimental physiopathology and after pharmacological treatments. Desipramine modified the catalytic properties of energy-linked enzymes differentially respect to the types of intra-synaptic mitochondria, explaining at subcellular level and on functional proteomic basis the previously observed conflicting results about ADs on mitochondria. In this research, Desipramine exerted on the energy metabolism distinctive effects on post-synaptic compartment and on pre-synaptic terminal: the present data allow to integrate from a bioenergetic point of view the pharmacodynamic features of this paradigmatic drug

Biography:

Prof. Dr. Chung has completed his PhD and postdoctoral studies from College of Medicine, Kyung Hee University, Seoul, Korea. He had the research fellowship from Division of Cerebrovascular & Endovascular surgery, Department of Neurologic surgery, Mayo Clinic, Rochester, Minnesota, USA. He is the Associate professor and Director of Division of Cerebrovascular & Endovascular surgery, Department of Neurologic surgery, Eulji University Hospital, College of Medicine, Eulji University, Daejeon, Korea. He has published more than 20 papers in reputed journals and has been serving as a reviewer board member of Journal of Cerebrovascular & Endovascular Neurosurgery and Journal of Korean Neurosurgical Society.

Abstract:

The main concern during transfemoral carotid artery stenting (CAS) is preventing cerebral embolus dislodgement. We compared clinical outcomes and intraprocedural embolization rates of CAS using a distal filter protection device or proximal balloon occlusion device. From January 2012 to March 2015, a series of 58 patients with symptomatic or asymptomatic internal carotid artery stenosis ≥70% were treated with CAS with embolic protection device in single center. All patients underwent post-CAS diffusion-weighted magnetic resonance im¬aging (DW-MRI) to detect new ischemic lesions. We compared clinical outcomes and postprocedural embolization rates. CAS was performed in all 61 patients. Distal filter protection success rate was 96.6% (28/29), whose mean age was 70.9 years, and mean stenosis was 81%. Their preprocedural infarction rate was 39% (11/28). Subsequent DW-MRI revealed 96 new ischemic lesions in 71% (20/28) patients. In contrast, the proximal balloon occlusion device success rate was 93.8% (30/32), whose mean age was 68.8 years and mean stenosis was 86%. Preprocedure infarction rate was 47% (14/30). DW-MRI revealed 45 new ischemic lesions in 57% (17/30) patients. Compared with distal filter protection device, proximal balloon occlusion device resulted in fewer ischemic lesions per patient (p=0.028). In each group, type of stent during CAS had no significant effect on number of periprocedural embolisms. Only 2 transient neurologic events occurred in the successfully treated patients (one from each group). Transfemoral CAS with proximal balloon occlusion device achieves good results. Compared with distal filter protection, proximal bal¬loon occlusion might be more effective in reducing cerebral embolism during CAS.

Biography:

Prof. Dr. Francisco Capani has completed his PhD at the age of 27 years from University of Buenos and postdoctoral studies from University of California San Diego, School of Medicine and Karolinska Institute, Department of Neuroscience. He is the vice director of Institute of Cardiologic Research, and Professor of Histology and Cell Biology, School of Medicine, University of Buenos Aires. He has published more than 75 papers in reputed journals and has been invited in more than 14 international symposium. He has been serving in the editorial in board of several scientific journal.

Abstract:

Thioredoxin (Trx) family proteins are a key mediator for different cell functions via regulation of the thiol redox state of several proteins and the levels of the second messenger hydrogen peroxide. Their modifications have been involved in various pathologies. Then the studied of the role of Trxs in neuronal recovery, following hypoxia/ischemia and reperfusion in both “in vitro” and “in vivo” model of perinatal asphyxia is important to understand the physiopathology of this disease. For that propose we have analyzed the distribution of 14 Trx family proteins in the cerebellum, striatum, and hippocampus. In addition we have perform a set of experiments to dissect the functions of some redoxins as suggested in vivo model of perinatal asphyxia in SH-SY5Y cells subjected to hypoxia and reoxygenation. Using both approaches, we have discovered a cell-type and tissue-specific expression pattern following the hypoxia/ischemia and reoxygenation. Specifically, Grx2 and Trx1 showed a particular deeply modifications during cell tissue recovery. Silencing of these proteins in SH-SY5Y cells subjected to hypoxia-reoxygenation strongly suggested that these proteins are related to maintain the normal neuronal and astrogial phenotype. These data demonstrate the significance of redox signaling in cellular pathways. Grx2 and Trx1 contribute significantly to neuronal integrity and could be clinically relevant in neuronal damage induced by perinatal asphyxia and its neurological deficits including delayed mental and motor development, epilepsy and major cognitive deficits. Therefore, redoxins give a unique opportunity for studying their role as therapeutic tools in a disease that up today does not have any efficient cure.

Biography:

There is a need to discuss the impact of Physical Education on cognitive performance (and give a possible explaination), because these programs are required to contribute to the primary mission of schools, i.e., the promotion of academic performance. This talk is devoted to understand how physical activity is related to neuroendocrinological alterations in adolescents and how these changes influence cognition and motor control or coordinative skills. The results of the studies presented here are good to develop methods for improving the effectiveness of physical activity interventions by tailoring them to account for individual benefits in academic performance in schools. The results will lead to the conclusion that acute physical activity enhances cognitive performance, and, at the same time, affects the release of steroid hormones. Consequently, the shift in hormone concentration is jointly responsible for cognitive changes. Often, reports in support of the association of physical activity and cognitive performance as well as steroid hormones are backed by data from adults. For this reason, we collected data from children and adolescents that reasonably complement the triangular effect of acute exercise – cognitive performance – concentration of steroid hormones. We will provide evidence to promote this relation as well as examples how to apply this results in a school setting. The talk will end with the results of a longitudinal study we recently conducted which deals with the effect of additional exercise training on cognitive functioning, emotional parameters and hormonal functions.

Abstract:

There is a need to discuss the impact of Physical Education on cognitive performance (and give a possible explaination), because these programs are required to contribute to the primary mission of schools, i.e., the promotion of academic performance. This talk is devoted to understand how physical activity is related to neuroendocrinological alterations in adolescents and how these changes influence cognition and motor control or coordinative skills. The results of the studies presented here are good to develop methods for improving the effectiveness of physical activity interventions by tailoring them to account for individual benefits in academic performance in schools. The results will lead to the conclusion that acute physical activity enhances cognitive performance, and, at the same time, affects the release of steroid hormones. Consequently, the shift in hormone concentration is jointly responsible for cognitive changes. Often, reports in support of the association of physical activity and cognitive performance as well as steroid hormones are backed by data from adults. For this reason, we collected data from children and adolescents that reasonably complement the triangular effect of acute exercise – cognitive performance – concentration of steroid hormones. We will provide evidence to promote this relation as well as examples how to apply this results in a school setting. The talk will end with the results of a longitudinal study we recently conducted which deals with the effect of additional exercise training on cognitive functioning, emotional parameters and hormonal functions.

Biography:

Robert Zorec is Professor of Pathophysiology at the University of Ljubljana, Medical Faculty, a Full Member of Academia Europaea (London) and Slovenian Academy of Sciences and Arts (cont. of Academia Operosorum Labacensis from 1693), as well as a Past Member of the Committee for Advanced Medical Products at the European Medicine’s Agency (London). He received his PhD from the University of Ljubljana in 1986 for his work conducted at the Newcastle Medical School and at the MRC Neuroendocrinology Unit in Newcastle upon Tyne, UK, and introduced the "patch-clamp" method in Ljubljana in 1985. His Postdoctoral experience was at Cambridge in Dr W T Mason's laboratory. In addition to basic research focusing into physiological and pathological problems, the lab is also developing advanced cell-based medicines such as hybridoma cells to treat cancer, a product HybriCure® is currently in clinical trial. His work was and is supported by different grants from EU and other countries (the British Council and The Wellcome Trust Fellowships, Fulbright Scholarship, Research Council of Slovenia, Nuffield Foundation, EduGLIA, NIH).

Abstract:

Astrocytes are the most heterogeneous glial cell type in the brain. Initially, they were considered to be merely “nervenkitt” as proposed by Virchow in 1858, playing only subservient roles to neurons. However, in the last two decades, it is clear that these cells provide key homeostatic functions to brain. As in other eukaryotic cells, astrocytic vesicles have key cellular functions including constitutive housekeeping of the plasma membrane structure and cell-to-cell communication. Vesicle traffic is associated with cell surface morphology exhibiting distinct glial microdomains. These determine the signaling potential and metabolic huby for neighboring cells. Moreover, vesicles are used in astrocytes for the release of vesicle-laden chemical messengers. It is now clear that this process, regulated exocytosis, is orders of magnitude slower than that found in neurons. This lecture will address the properties of membrane-bound vesicles that store secretory gliosignal molecules, other recycling vesicles, and endocytotic vesicles that are involved in the traffic of plasma membrane receptors such as the class II major histocompatibility molecules and membrane transporters (aquaporin 4 and excitatory amino acid transporter 2). Vesicle dynamics depends on intermediate filaments therefore one has to consider that altered vesicle traffic may be associated with the diseases such as amyotrophic lateral sclerosis, multiple sclerosis, autistic disorders, Alzheimer’s disease, trauma, edema, and states in which astrocytes contribute to neuroinflammation. Indeed, in multiple sclerosis, for example, fingolimod, a recently introduced drug, apparently also affects vesicle traffic and gliotransmitter release from astrocytes, indicating that this process may well be used as a pharmacologic target for the development of new therapies.

Biography:

David K Grandy, after receiving his PhD in Microbiology and Public Health from Michigan State University in 1985, joined Oregon Health & Science University’s Vollum Institute as a Post-doctoral research fellow, becoming a Principal Investigator in 1993. He was an Assistant Professor of Cell & Developmental Biology between 1992-1998, and then he was promoted to Associate (1998), then Full (2006) Professor of Physiology & Pharmacology in the School of Medicine. He has published 196 papers (63 Scopus ‘h’ Index); been awarded 22 US Patents; and served on several NIH Study Sections and editorial boards. In 2009, he was elected a Fellow of the Amreican College of Neuropsychpharmacology.

Abstract:

Originally known only to late 19th century chemists and students of fermentation and putrefaction, the noncatecholic biogenic amines (NBAs) entered the scientific main stream in the first decade of the 20th century with Barger and Dale’s groundbreaking studies demonstrating the profound pressor properties of -phenylethylamine and p-tyramine. However, unlike their close relatives the catecholamines, NBAs came to be regarded as ‘false transmitters’ and it would be nearly a century before these so-called ‘trace amines’ had a receptor of their own. Reported independently in 2001 by two groups the G protein-coupled receptor, now referred to as trace amine-associated receptor 1 (TAAR1), is the best-characterized member of a human gene family consisting of 9 members. Depending on the cellular environment heterologously expressed TAAR1 couples to cAMP production, mobilization of intracellular calcium, and chloride conductance. Unexpectedly, TAAR1-mediated signaling is constitutive exerting an inhibitory tone on mouse midbrain dopamine neurons. The capacity to express TAAR1 in vitro and the ability to assay its activation in multiple ways resulted in the compilation of a comprehensive pharmacological profile that challenges current concepts regarding the mechanism of action of several medically important drugs including amphetamine, methamphetamine, Ecstasy, apomorphine, and dopamine and its supposed inactive metabolite, 3-methoxytyramine. Given its pharmacological profile and anatomic distribution commercial high throughput screening efforts were initiated and several TAAR1-selective compounds were identified. With these new tools the receptor’s basic biology can now be explored in intact animals and the clinical value of pharmacologically manipulating its signaling in the context of mental health, evaluated.

Biography:

Ranjana Arya completed PhD in the field of Life Sciences from Jawaharlal Nehru University followed by Postdoctoral research experience at Harvard Medical School, Boston, USA and University of North Carolina, Chapel Hill, USA. He worked as Senior Research Scientist in pharmaceutical industry, Ranbaxy Research Laboratories, India for more than 3 years. Presently, he is Assistant Professor at School of Biotechnology, JNU since 2008. He has published 18 papers in reputed journals and guided 5 PhD research scholars as supervisor of which 1 has been awarded degree and other has submitted the thesis.

Abstract:

Biological basis of pathogenesis of a large number of genetic disorders is not known, particularly for those diseases which affect neuro-muscular system. UDP-GlcNAc 2-epimerase /ManNAc kinase (GNE) is a bifunctional enzyme (N-terminal epimerase and C-terminal Kinase domain) that catalyzes rate limiting step in sialic acid biosynthesis. Homozygous misssense mutations in either epimerase or kinase domain of GNE leads to slowly progressive autosomal recessive genetic neuromuscular disorder, Hereditary Inclusion Body Myopathy (HIBM)/Distal myopathy with rimmed vacuoles (DMRV). These GNE related myopathies are characterized by hyposialylation of glycoproteins in muscle cells of patients and primary defect in either N or O-linked glycosylation. However, it appears from some recent experiments including those from our laboratory that mutant GNE may also affect targets that are not directly related to sialic acid biosynthesis. In particular cytoskeletal network, sarcomere organization and apoptotic signaling are likely to be altered in muscle cells. In absence of clear understanding of the pathomechanism, no treatment is currently available to cure the disease. Our laboratory focuses on deciphering alternate roles of GNE in regulating cell functions with an aim to identify more effective drug targets. We have established a HEK293 cell based assay system where pathologically relevant mutations of GNE are overexpressed alongwith GNE knockdown using shRNA. The system is validated by reduced sialic acid content of the cell and restoration of sialylation after supplementation with 5 mM sialic acid. Using this system, GNE has been shown to affect cell adhesion property via hyposialylation of β-1 integrin. This leads to increased binding of cell to fibronectin and activation of FAK/Src/paxillin to promote focal adhesion assembly. The cytoskeletal network is altered due to misbalance in G-actin and F-actin levels in GNE deficient cell lines. Interestingly, mutation in GNE causes increased apoptosis via mitochondrial dysfunction. The ultrastructure of mitochondria was found to be altered in GNE mutant cells along with disruption of membrane potential. In addition, total reactive oxygen species (ROS) were found to be altered indicative of oxidative stress generation. Our study clearly provides a base for understanding pathomechanism of GNE myopathy and the opportunity of using cell-based assay for exploring pharmacological drug molecules.

Biography:

Abstract:

G-Protein Coupled Receptors (GPCRs) are major contributors to the information flow into cells and, as such, are involved in a wide range of physiological processes and diseases, including those affecting the cardiovascular, nervous, endocrine, and immune systems. Therefore, GPCRs are potential druggable targets (60-70%) in a multitude of therapeutics areas. Moreover, GPCRs represent more than one third of the targets for currently marketed drugs. The structures of GPCRs needs to be elucidated in order to employ them in drug design and discovery, using the methods of “Structure Based Drug Design” (SBDD). Direct experimental study of GPCR structures is currently difficult because of the native membrane environment, which poses limitations to the purification and crystallization process. High resolution structural information is available only for ~2% of the GPCRs. Based on statistical analysis of (Y)/Phi (F) and RMSDs (Root Mean Square Deviation) of the trans-membrane domains, some tips are presented to make easier modelling GPCRs finally getting reliable models. Serotonergic system modulation may present a promising strategy for slowing AD progression and improving cognition. Increasing serotonin (5-HT) signaling and developing molecules that enhance 5-HT concentration in the synaptic cleft have been debated as possible therapeutic strategies to slow the progression of Alzheimer’s disease. A model of a membrane bound G-protein system to study all the mechanisms involved in the 5-HT7 activation will be presented. These findings could be exploited to rationally design new ligands to selectively regulate different transduction pathways underlying a number of different disorders.

Biography:

Eliyahu Dremencov has completed his PhD from Bar-Ilan University in Ramat-Gan (Israel) and Postdoctoral studies from the University of Ottawa Institute of Mental Health Research (Ontario, Canada). He is the Director of Neuroken Consulting, a biomedical R&D consulting firm based in Groningen, the Netherlands, and an independent research scientist in the Institutes of Molecular Physiology and Genetics and Experimental Endocrinology of the Slovak Academy of Sciences in Bratislava. He has published more than 40 papers in reputed journals and has been serving as an Editorial Board Member. He has served as an expert consultant for the Medical Research Council of the UK, National Research Agency of France, Research Executive Agency of the European Union, Department of Health and Human Services of the US, and Ministry of Education and Science of the Russian Federation.

Abstract:

Depression and related mood and anxiety disorders affect, at least once in a lifetime, about one third of the world population. These disorders are considered to be the second major reason for disability in the industrial countries and they are estimated to become the second major reason for disability worldwide within 20 years. Despite relative progress with the development of novel antidepressant, anxiolytic, and mood stabilizing medications, their efficacy remains limited. Almost all antidepressant drugs act on monoamine (serotonin: 5-HT, norepinephrine: NE, and dopamine: DA) systems of the brain. Although monoamines play a central role in pathophysiology and treatment of depression, it is possible that other brain systems should be targeted as well, in order to achieve the better outcome of the treatment. One of such targets is brain histamine. Although histamine play an important role in the regulation of the mood and cognition, its potential role in mood disorders received limited attention. The recent studies, however, report that the certain histamine agents, such as antagonists of histamine-3 (H3) receptors, stimulate 5-HT, NE and DA neurotransmissions and might be therefore used in the treatment of depression. Another potential target is adenosine. Since the aggregation of neurotransmitters into the synaptic vesicles requires adenosine triphosphate (ATP), adenosine, as a product of ATP metabolism, is co-released, together with the “main” neurotransmitter, from all brain neurons. Brain neurons express receptors for adenosine, which indicates that adenosine play a role in neural transmission rather than just being a co-product of the aggregation process. The recent studies demonstrated that adenosine-2A (A2A) receptors interact, on molecular and functional levels, with dopamine-2 (D2) and alpha-2 (α2) adrenergic receptors, and A2A antagonists might be used in the treatment of certain brain disorders. Finally, hypothalamic neuropeptides, such as β-endorphin, neuropeptide Y, oxytocin and vasopressin, playing an important role in reward, emotional processing, and stress response, might be a promising target for the development of novel antidepressant and mood stabilizing treatments.

Biography:

Costanza Burattini completed her undergraduate thesis at UCSF, where she worked as a lab technician for 2 years. In 2007, she completed her PhD in Neurophysiology from the University of Bologna; during her PhD course she spent 1 year at the Mario Negri Institute of Pharmacological Research in Milan. After completing her Post-doctoral studies at the University of Bologna, she currently works as a Research Associate at the same institution.

Abstract:

The nucleus accumbens (NAc), a ventromedial component of the mesocorticolimbic dopamine system, plays a pivotal role in the mediation of motivation and reward, drug addiction, learning, feeding and mood disorders. This brain area receives dopaminergic inputs from the ventral tegmental area, glutamatergic afferents from cortical and sub cortical limbic structures and a dense serotonergic innervation from dorsal raphe nucleus neurons. Glutamatergic synapses within the NAc can express plasticity, including endocannabinoid (eCB)-long-term depression (LTD); eCBs are arachidonic acid-derived lipid signaling molecules acting at CB receptors. Anatomical studies have shown that CB1 receptors are located presynaptically on glutamatergic neurons in the NAc, and that they participate in the regulation of transmitter release. Recent evidences demonstrate an extensive co-localization of CB1 and 5-HT receptors within the NAc suggesting the potential for interplay between them. In the present study, performed in a rat slice preparation containing the NAc, we found that prolonged (20 min) low-frequency (4 Hz) stimulation (LFS-4Hz) of glutamatergic afferences induces a novel form of eCB-LTD in the NAc core, which requires 5-HT2 and CB1 receptors activation and L-type voltage-gated Ca2+ channels (VGCC) opening. Present results suggest that LFS-4Hz induces the release of 5-HT, increases Ca2+ influx through VGCC and e-CB production and release; the eCB travels retrogradely and binds to presynaptic CB1 receptors, causing a long-lasting decrease of glutamate release resulting in LTD. These observations might be helpful to understand the neurophysiological mechanisms underlying drug addiction, major depression and other psychiatric disorders characterized by dysfunction of 5-HT neurotransmission in the NAc.

Biography:

Mr. Abdul Khayum. K is a Assistant Professor in department of pharmcology at Karpagam University, India. He has completed his Bachelor of Pharmacy from Calicut University, Kerala, India and his Masters at the age of 25 from The Dr. M.G.R medical university, Tamilnadu, India. His PG dissertation work involves role of low dose of L-Glutamic acid administration in global ischemic model. During his PG work he learnt surgery procedure for ischemic induction, handled laser perfusion imager to measure cerebral blood flow and experienced in animal behavioral studies. As a young researcher his paper was accepted in Behavioural Pharmacology Journal and is under revision.

Abstract:

The present study has been designed on the hypothesis that administration of low dose of glutamate in cerebral ischemia might attenuate the excitotoxicity in neurons through its pre-synaptic auto-receptor regulatory mechanism, rather than the intensification of neurodegenerative conditions. To test the hypothesis, the effect of L-Glutamic acid 400μM/kg (L-GA) was evaluated in bilateral common carotid artery occlusion (BCCAo) induced global ischemic mice model. Global ischemia in mice was induced by occlusion of both the common carotid artery (BCCAo) for 20 min followed by reperfusion injury. L-GA was infused slowly through the tail vein, 30 min before the surgery, and every 24 hrs thereafter, until the experiment was completed. The time dependent change in the cerebral blood flow (CBF) was monitored using Laser Doppler image analyzer. The neurotransmitters and neurobiochemicals were measured in the different regions of brain at 0, 24, 48, and 72 hrs respectively after reperfusion injury. The results have shown that administration of L-GA increased the locomotor activity, muscle co-ordination, and CBF in ischemic mice at 72 hrs after ischemic insult in comparison to 24 and 48 hrs. L-GA administered group exhibited significant reduction in the glutamate level in cortex, striatum, and hippocampus regions at 72 hrs whereas gamma aminobutyric acid (GABA) levels were elevated in all three brain regions studied. Further, it elevated the glutathione (GSH) level and attenuated the nitric oxide (NO) content, but failed to restore the adenosine tri-phosphate (ATP) level after 72 hrs of IR. Memantine (MN) has been used as the standard drug. The study concludes that the gradual reduction of glutamate along with elevation of GABA in different brain regions may have contributed the neuroprotective effect of L-GA. Hence slow infusion of ultra low dose of L-GA could be beneficial in controlling excitotoxicity neurodegeneration in ischemia conditions.

Biography:

Nachum Dafny received his MS and PhD degrees from Hadassah Medical School in Jerusalem in 1965 and 1969, respectively followed by post-docs at Caltech, UCLA, and Columbia. He is currently a Professor of Neurobiology at the University of Texas Medical School at Houston.

Abstract:

The prefrontal cortex (PFC) is involved in complex planning, learning, memory, attention and integrates sensory information. It was reported that the PFC is dysfunctional in attention deficit hyperactivity disorder (ADHD). Methylphenidate (MPD), a drug often prescribed for the treatment of ADHD, has potential for abuse and misuse. Most MPD studies were completed in adult subjects; however most users are adolescents. The objective of this study was to investigate the acute and chronic dose response characteristics of MPD on PFC neuronal activity recorded in freely behaving adolescent rats. Four groups of animals were used: saline (control), 0.6, 2.5, and 10 mg/kg MPD. Acute MPD elicited a dose response increase in animals’ locomotor activity. Rechallenge with MPD at experimental day (ED10) when compared to the effect of MPD at ED1 showed no significant differences. When the animals were divided into two groups based on their individual responses to chronic MPD exposure, some animals expressed behavioral tolerance and some expressed behavioral sensitization. Electrophysiologically, a dose response characteristic for acute and chronic MPD exposure was observed. With increasing MPD doses, more PFC units responded by changing their firing rate. Moreover, the neuronal responses to chronic MPD recorded from animals expressing behavioral tolerance were significantly different compared to the neuronal population responses recorded from animals expressing behavioral sensitization. The majority of the PFC units recorded from animals expressing behavioral tolerance responded to MPD predominately by decreasing their firing rates, whereas PFC units recorded from behaviorally sensitized animals mainly showed an increase in their firing rates.

Biography:

Carola Forster has completed her PhD from Hannover University in Germany and Salamanca University in Spain and Post-doctoral studies from SUNY Upstate University, Syracuse, NY, USA and Karolinska Institute, Stockholm, Sweden, Schools of Medicine. She is the Head of Department of Experimental Anesthesiology at Würzburg Clinic of Anaesthesia and Critical Care. She has published more than 55 papers in reputed journals and has been serving as an Editorial Board Member of repute.

Abstract:

The microenvironment of the central nervous system (CNS) is maintained by the blood brain barrier (BBB) which is made up of brain capillary endothelial cells. Injury or damage compromises BBB integrity. Traumatic brain injury (TBI) results from an outward impact that causes immediate mechanical disruption of brain tissue and delayed pathogenic events which collectively mediate widespread neurodegeneration. The initial impact is usually followed by the development of secondary injury as a result of cerebral ischemia which leads to brain swelling and edema, activation of inflammation and BBB leakage. Although several models for studying the mechanisms of TBI exist, no single system covers all the spectrum of events that might occur during TBI. Thus, in an attempt to include both the initial outward injury during TBI and the secondary injury as a result thereof in one model system, we established an in vitro TBI model using stretch in combination with oxygen-glucose deprivation (OGD). Using this model, the effects of ischemia and TBI to calcium levels and inflammatory response in the BBB through the brain microvascular endothelial cell cEND were investigated. Results show that damage to cEND cells leads to increased lactate dehydrogenase enzyme (LDH) and nitric oxide (NO) release into the cell. Moreover, mRNA expression of inflammatory markers interleukin (IL)-6, IL-1α, chemokine (C-C motif) ligand 2 (CCL2) and tumor necrosis factor (TNF)-α also increased. This inflammatory cascade triggers the opening of calcium ion channels demonstrated by increased calcium levels in cEND cells subjected to OGD and incubated with astrocyte-conditioned medium.

Biography:

Abstract:

Gene expression studies employing real-time PCR has become an intrinsic part of biomedical research. Appropriate normalization of target gene transcript(s) based on stably expressed housekeeping genes is crucial in individual experimental conditions to obtain accurate results. In multiple sclerosis (MS), several gene expression studies have been undertaken, however, the suitability of housekeeping genes to express stably in this disease is not yet explored. The present study aims to evaluate the expression stability of a panel of housekeeping genes in rat neurons and oligodendrocyte progenitor cells (OPCs) treated with cerebrospinal fluid derived from MS patients. For neurons, reference genes chosen from literature were quantified by real time PCR and their expression stability was assessed using geNorm and NormFinder algorithms. For OPCs, reference genes were chosen from microarray data and their stability was assessed using similar algorithms. Both algorithms revealed transferrin receptor (Tfrc) and microglobulin beta-2 (B2m) the most stable genes followed by ribosomal protein L19 (Rpl19) in neurons whereas beta-actin (ActB) and glyceraldehyde-3-phosphate-dehydrogenase (Gapdh) the most fluctuated ones. On the contrary, geNorm revealed mitochondrial ribosomal protein L19 (Mrpl19), hypoxanthine phosphoribosyl transferase (Hprt) and microglobulin 2 (B2m) as the best housekeeping genes and Gapdh the least stable in CSF exposed OPCs. Altogether our data demonstrate the significance of pre-validation of housekeeping genes for accurate normalization and indicates Tfrc and B2m as best endogenous controls in neurons and Mrpl19 and Hprt in OPCs treated with CSF from MS patients. ActB and Gapdh are not recommended in gene expression studies related to current one.

Biography:

Atsuyoshi Shimada has completed MD-PhD from Kyoto University School of Medicine. Based on his training in experimental pathology in Kyoto and clinical neuropathology at Columbia University, he has studied basic mechanisms underlying brain aging, neurodegeneration, neuronal development and excitotoxic neuronal injury as well as roles for lipid mediators in the brain. His present research interest is in how the brain and immune system interact with each other by way of cell dynamics and intercellular chemical mediators. He has a concept that such brain-immune interaction is a bioregulatory mechanism and its disturbances cause a variety of psychiatric and neurological diseases.

Abstract:

The immune system modulates higher functions of the brain under non-inflammatory conditions. However, how immune cells interact with brain parenchymal cells remains to be determined. Using bone marrow chimeric mice in which the recipients’ immune system was reconstituted by marrow cells derived from GFP-transgenic mice by syngeneic intra-bone marrow-bone marrow transplantation (IBM-BMT), we examined the distribution, density and differentiation of donor-derived marrow cells in the brain parenchyma 2 weeks and 1, 4 and 8 months after IBM-BMT. Marrow-derived cells started to populate discrete brain regions from 1 to 4 months after IBM-BMT, exhibited ramified morphology and expressed Iba-1, indicating the myeloid lineage. Most of these discrete regions were adjacent to the attachments of choroid plexus that comprised thinned brain parenchyma consisting of astrocytic processes in the narrow channel between the ependyma and pia. These specific portions of astrocytic processes expressed CX3CL1, a myeloid cell-attracting chemokine. In the choroid plexus stroma, not only Iba-1-immunopositive myeloid cells but also non-myeloid CXCL12-expressing cells were of bone marrow-origin. Transcripts of CX3CL1, CXCL12 and their related molecules such as CX3CR1, ADAM10 and CXCR4 were detected in the tissue consisting of the choroid plexus, the attachments and adjacent brain parenchyma. Thus, bone marrow cells selectively enter the discrete brain regions via the attachments of choroid plexus and differentiate into ramified myeloid cells. CX3CL1 in the attachments of choroid plexus and CXCL12 in the choroid plexus stroma may be involved in these brain-immune interactions.

Biography:

Kaveh Shafiei is Assistant Neurologist from Kerman University of Medical Sciences in Iran. He is the deputy of education at the Shafa Hopital, an university based hopital . He has published 5 papers in reputed journals and has been serving as Scientific commitee member of 2 international gathering in Kerman.

Abstract:

Background: Topiramate is an approved and effective drug in migraine prophylaxis. Paresthesia is the most commonly reported side effect. The primary objective of this study was to compare the frequency of Topiramate induced paresthesia in migraine headache to Epileptic patients. Methods: Patients with migraine without aura and epilepsy were enrolled in this observational study. All cases were interviewed by telephone about their history of paresthesia. Confounding factors were controlled through logistic regression. Results: The odd ratio of developing Topiramate induced paresthesia in migraine compared to epilepsy patients was to 3.4. Three factors were independent contributors to developing Topiramate induced paresthesia, female sex (Odd ratio 2.1), Topiramate dosage (odd ratio 0.3) and duration of therapy. Conclusion: Our findings indicate an independent association between migraine and development of paresthesia. Migraineurs were more likely than epileptic patients to report paresthesia as Topiramate adverse effects. Female sex, treatment duration and Topiramate dosage contribute significantly to subsequent development of paresthesia.

Biography:

Maria Alexandra Brito has completed her PhD in 2001 and the Habilitation degree in 2012, at the University of Lisbon, Portugal. She is the Head of the Nerovascular Laboratory, within the Neuron Glia Biology in Health and Disease Unit of the Research Institute for Medicines (iMed.ULisboa). Her research activity has been devoted to the study of the underlying mechanisms of frequent pathologies of the neonatal and aging life, like neonatal jaundice and Alzheimer’s disease, respectively. Currently, her studies have been focused in the blood-brain barrier, aiming at understanding the vascular events associated to such disorders of the central nervous system, identifying early biomarkers of neurologic affliction and revealing targets for modulation for future therapeutics.

Abstract:

The blood-brain barrier (BBB) is a complex and dynamic interface between blood and brain that strictly controls the exchange of molecules between peripheral tissues and the central nervous system (CNS), thus playing a key role in brain homeostasis and in its protection against toxic compounds and pathogenic agents. The unique properties of brain capillaries are determined by complex interactions between brain microvascular endothelial cells, the basement membrane, the pericytes and astrocyte feet, also involving neurons and microglia that altogether form the neurovascular unit. The emerging role of the BBB in the progression of brain disorders will be presented, based on our own studies focused on neonatal jaundice, the most common clinical condition of the neonatal period, as well as on Alzheimer’s disease, the most prevalent age-associated neurologic disorder. Based on in vitro and ex vivo studies, evidence will be provided that behind neural and glial dysfunction there are marked alterations of brain microvascular endothelial cells and pericytes, as well as of the basement membrane, that collectively contribute to disruption of BBB properties. Collected data suggest that the “neurocentric” view should give place to a broader view including the “neuro-glio-vascular triad” in order to consider the several intervenients in the pathogenesis of these pathologies so common in the neonatal and elderly periods of life.

Biography:

Dr. Gajender Singh Ranga has completed his MBBS at the age of 23years from MD University Rohtak and completed his MD from prestigious All India institute of medical sciences, Delhi-110095. He is consultant of Medicine for last 20 years and currently acting as Director Professor in Deptt of Medicine at Guru Teg Bahadur Hospital and University college of Medical Sciences, Delhi-110095, India. He has published more than 25 papers in reputed journals and has been serving as an editorial board member of Journal of advanced research in Medicine.

Abstract:

Human carcinoembryonic antigen (CEA) is a tumour marker used to diagnose various malignanacies. Striking similarties have been reported between process of tumourigenesis and atherosclerosis. CEA has been reported a useful biomarker for diagnosis of acute coronary syndrome whose pathogenic mechanism is is rupture of atherosclerotic plaque. Although, same pathogenic mechanism leads to ischemic stroke, the role of CEA for diagnosis of acute ischemic has not been evaluated so far. We are the first one to conduct this pilot study and found CEA to be a very useful biomarker for diagnosis of acute ischemic stroke as well. Although ,CT scan and MRI have taken big step forward towards diagnosis of acute ischemic stroke, early diagnosis is still a major challenge. Moreover , these facilities are not available at every centre and sometimes their results may be false negetive. In these circumstances and for early diagnosis of acute ischemic stroke CEA has been found to be a very useful biomarkes by us. Our results are encouraging, as for diagnosis of acute coronory syndrome several useful diagnostic markers are available but for early diagnosis of acute ischemic stroke only few have been reported and they are not very robust and not widely used. Our stringent exclusion criteria further make our study result remarkable.The results of our study will be discussed in detail.

Biography:

Marija Knezevic-Pogančev has completed her PhD from University and Postdoctoral studies from Novi Sad University School of Medicine. She is Pediatrician, Clinical Neurophysiologist and Epileptologist, and Sub-Specialist for neurology and psychiatry of developmental age. She has published more than 125 papers 11 in reputed journals.

Abstract:

Epileptic Spasms (ES) in West Syndrome (WS) are a specific type of attack with a unique clinical and Electroencephalographic (EEG) pattern. Reanalyzing only EEGs for 25 followed for at least 10 years in Child and Youth Health Care Institute of Vojvodina symmetrical spasms were present in both cryptogenic and at symptomatic WS, while the asymmetric spasms and focal epileptic spasms characteristics indicate brain lesion. Positive vertex slow waves EEG pattern were present in both groups. Fast activity resembling a spindle corresponds with absence while electro-decremental activity presents postictal. Lateralized slow activity is significantly more common among symptomatic WS with a poor prognosis and structural brain lesions. Consistent fast beta activity EEG ictal lateralization is significantly more common among children who show resistance to initial therapy. Fat low voltaged activity often progress with the development of epileptic encephalopathies, indicating cortical dysfunction. Although independent of WS etiology, hypsarrhythmia that persists during ES series indicates a good prognosis.

Biography:

MF Suaud-Chagny is Research Director appointed by INSERM (National Institute of Health and Medical Research) and the head of the team PSYR2 – Psychiatric Disorders: from Resistance to Response, a team integrated into the Lyon Neuroscience Research Center (France). MF Suaud-Chagny has authored more than 55 papers in peer-reviewed journals. Her areas of expertise include psychiatry, therapeutic development and translational research with a specific focus on dopaminergic transmission. She has teaching, lecture and supervising experience at the undergraduate, graduate and medical school levels and ad hoc reviewer activities for journals and for grants for national and international agencies

Abstract:

MAP6 (microtubule-associated protein 6) KO mouse is a microtubule-deficient model that exhibits severe behavioural and biological alterations reminiscent of schizophrenia. Total deletion of MAP6 gene in mice leads, in adulthood, to behavioural disorders related to positive and negative symptoms and to cognitive impairments seen in schizophrenia. The strong behavioural phenotype of MAP6-KO mice may be the consequence of the many biological dysfunctions seen in these mice and known to be implicated in schizophrenia, such as nervous system plasticity impairments and alterations in many neurotransmission systems. Some of these behavioural and biological defects are sensitive to antipsychotics but also to microtubule-modulator molecules. A decreased expression of MAP6 proteins in heterozygous (Het) mice results in a blunted phenotype compared to MAP6-KO mice, corroborating that the dosages of susceptibility genes modulate their putative phenotypic contribution. Het mice displayed behavioural deficits strongly arguing for a high penetrance of MAP6 mutation in cognition. Human studies propose cognitive deficits in ultra-high-risk populations as robust premorbid predictive markers of a subsequent psychotic disorder. We propose MAP6-Het mouse as a translational animal model for the genetic ultra-high-risk states of schizophrenia. The validity of the model is supported by the exacerbation, through maternal deprivation, of the behavioural alterations related to positive symptoms. Such a model will help to elucidate transition factors from ultra-high-risk states to full-blown psychosis and to decipher the mechanisms underlying this transition. Because cognitive deficits in ultra-high-risk populations have been proposed as targets for early intervention, MAP6-Het mice would be valuable tools to study preventive strategies.

Biography:

Dr. Patrizia Proia has completed his PhD in Neuroscienze at the age of 34 years from Palermo University and postdoctoral studies on perfoming enhancing of anabolic androgenic steroids from University of Maryland. She is an assistant professor in biochemestryand she has published more than 20 papers in reputed journals and has been serving as a reviewer of repute. She now start a new multidisciplinary approach in order to analyze the effect of the exercise in patological and healthy people investigating the neurobiology response (on neurotrophines, hormones and protein stress related), genetic background and psycological assessment.

Abstract:

The aim of this study is to investigate the neurobiology of stress/emotionality, creating a multidisciplinary assessment model, which can help to provide psychological and physiological responses depending on the genetic background related to sport performances, social closeness and performance anxiety management in team sports. We enrolled 20 female volleyball players aged 13 ± 1 years old played in two different teams during a regional championship final. Saliva collection was carried out before and after the match. In order to evaluate the neuroendocrine effectors involved in stress and performance, we analyzed cortisol and progesterone levels through Elisa standard kit as well as HSP70 and amylase activity as stress-induced markers. As concern the psychometric assesment, we administrated he CSAI-2 test, Closeness Generating Procedure and STAI test. Genomic DNA was isolated from saliva cells using a QIAamp saliva kit according to the manufacturer’s protocols. The SNP of the 5-HTTLPR, BDNF, DRD4 were analyzed. The results of the T-test performed on the total results showed a statistically significant relationship (p < 0.05) in cortisol levels pre and post match, as well between amylase and HP70 according to the genetic background. The analysis performed using just post match samples show a negative correlation between social closeness, cortisol and progesterone levels, with p < 0.010 for progesterone vs social closeness and p < 0.012 for cortisol vs social closeness. About the winner teams and the looser teams, there is a negative correlation between pre match cortisol levels and performance anxiety (p < 0.042).

Biography:

Alessandro Ieraci has completed his PhD at University of Piemonte Orientale (Italy) and the post-doctoral training at the WMC of Cornell University, New York (USA). In 2007, he joined the Newron Pharmaceuticals with the goal of setting up animal models to study the efficacy of potential antipsychotic, antidepressant and cognitive enhancer drugs. Since 2011 is Research Associate at the Department of Pharmaceutical and Biomolecular Sciences, University of Milan (Italy), investigating the role of epigenetic mechanisms in the transcriptional modulation of neurotrophic factors, in response to environmental and pharmacological treatments. He has published more than 24 papers in reputed journal.

Abstract:

Physical exercise (PE) is an affordable and effective method to improve cognitive functions, mood and to prevent the stress-induced brain dysfunctions, partly by involving the action of brain-derived neurotrophic factor (BDNF). Although epigenetic modifications play a pivotal role in the regulation of the different BDNF transcripts, it is poorly understood whether both PE and stressful experiences modulate BDNF expression by epigenetic mechanisms. Moreover, a substantial variability of individual responses to PE and stressful experiences has been described. The reason for this is not known, but could be accounted for, among others, by individual genetic variants. We have found that PE and restraint stress (RS) have a complementary effect in controlling the total BDNF mRNA levels and specific BDNF transcripts expression in the hippocampus. Moreover, PE and RS differentially modulate the levels of histone H3 acetylation at the BDNF promoters and the histone deacetylases mRNA levels in the hippocampus. Interestingly, pretreatment with histone deacetylases inhibitors has similar efficacy as PE in preventing stress-induced down-regulation of BDNF transcripts. Remarkably, we have also found that PE-induced up-regulation of BDNF protein and BDNF transcripts are impaired in the knock-in mouse carrying the human BDNF Val66Met polymorphism. These deficiencies are accompanied by reduced PE-induced anxiolytic- and antidepressant-like response in BDNF Val66Met mutant mice. Overall, these results suggest that PE and RS are able to modulate complementary the expression of BDNF transcripts by different epigenetics mechanisms; and that the human BDNF Val66Met polymorphism impairs the PE-induced beneficial effects in mice.

Biography:

Mariagrazia Grilli received her MD in 1987 at the University of Brescia, Italy. Since 2005, she is Associate Professor of Pharmacology, at University of Piemonte Orientale, Novara, Italy, where she directs the laboratory of Neuroplasticity, working on the potential contribution of adult neurogenesis, when disregulated, to neuropsychiatric conditions. As a pharmacologist, her current research activities are aimed at understanding whether adult neural stem cells and their neuronal/non neuronal progeny may represent innovative targets for new chemical entities but also for drugs already in clinic, whose novel properties may potentially help their repositioning and increase our understanding of their therapeutic effects.

Abstract:

Although the role of adult hippocampal neurogenesis remains to be fully elucidated, a vast array of data suggest that this process is involved in cognitive and emotional functions and deregulated in various neuropsychiatric disorders, including major depression. An intriguing area of interest for pharmacologists is the influence of psychoactive drugs on adult neurogenesis. In particular, several authors have contributed to the idea that antidepressant-induced increase in hippocampal neurogenesis is required for at least some of the drug behavioural effects in rodent and primate models. Altogether these data have led to the hypothesis that the positive modulatory effect of antidepressants on hippocampal neurogenesis may, at least in part, contribute to the therapeutic effects of antidepressants in patients. Among molecular participants which could regulate adult neurogenesis the NF-κB family of transcription factors has been receiving particular attention from our and other laboratories. In particular, our recent data supported the idea that the NF-κB signalling pathway may play an important regulatory role in adult hippocampal neurogenesis both in physiological and pathophysiological conditions. Furthermore we discovered that NF-κB signalling may be potentially involved in mediating the novel proneurogenic and antidepressive-like activity of some clinically relevant drugs, including α2δ ligands and acetyl-L-carnitine. The potential implications of these findings on our current understanding of the process of adult neurogenesis in physiological and pathological conditions and on the search for novel antidepressants will be discussed.

Biography:

Bouchra Oneib received her MD in 2008 at the university of Rabat. Since 2013, she is assistant professor of psychiatry at the university Mohammed I school of medecine , and preparing her PhD from the department of psychiatry. She is interested in the epidemiology of psychiatric diseases , their impact on the quality of life on patients and response to the psychotropic drugs

Abstract:

Depressive disorders are within the most prevalent mental disease worldwide. We know that 40–50% of depressed patients are detected in primary health care, and 20% receive adequate treatment. Early diagnosis can improve well-being of patients, ensure a better antidepressant response and reduce the risk of recurrence and suicide. The objective of the study is to determine the prevalence and the impact life of depressive disorders in primary health care and its associated factors. We conducted a cross-sectional study with 351 participants selected from Moroccan primary care facilities, aged above 18 years without chronic somatic or psychiatric disease. The participants answered a questionnaire that included demographic characteristics, the Mini International Neuropsychiatric Interview for major depressive episode (MDE), dysthymic disorder and the Global Assessment of Functioning (GAF). The prevalence of depressive disorders in the sample was 13.7%, that of MDE was 9.1%, while dysthymic disorder was 4.3%, and the prevalence of depression over a lifetime was 17.7%. Analysis of GAF scores showed an average of 76.2 ± 24, a lower score was significantly found among patients with current MDE (P = 0.001), dysthymic subjects (P = 0.001) and those who suffer from recurrent MDE (P = 0.001). Depressive disorders in univariate analysis were associated with: Female gender odds ratio (OR) 2.1 (1.09-4.3), unemployment OR 0.4 (0.2-0.9), and childbearing age OR 3.5 (1.5-8). The high prevalence of depressive disorders and the alteration of the quality of life among primary health care patients in Morocco suggest the importance of identifying and treating this population.

Biography:

Arjan Blokland studied Psychology in Nijmegen (NL) and graduated in 1987. After receiving his PhD in Maastricht in 1992, he did a post doc at the University of Cambridge in 1992. In 1993 he took a position as laboratory head at Tropon (CNS research Bayer). He was responsible for testing novel compounds in animal models of aging and dementia. In 1996 he retrurned to Maastricht University with a main focus on psychopharmacology of learning and memory. Since many years he has been involved in the evaluation of drugs on memory performance in animals and humans. The aim of these studies was also finding translational tools in examining the predictability of treatments in animals to humans. He has been working with various drug companies in characterizing newly developed drugs in animal models of learning and memory.

Abstract:

Many factors can complicate the translation from animal studies to human studies, especially relating to the development of cognition enhancers. First, models that are being used in animal experiments have a poor validity (e.g., construct validity). This relates to the deficit model that should reflect a disease model. Since these models can only mimic a specific aspect of a complex disease state it is not surprising that these models can only have a limited value when evaluating novel drugs. As a second factor, the face validity of animal test models is obviously rather poor when comparing these with memory tasks in humans. It is well known that there are species differences in PK/PD parameters, which is a third complicating factor. For example, the absorbtion of brain penetration is much faster in animals as compared to humans. It is known that this difference can have a different effct on brain functions. A fourth complicating factor may be related to the inverted U-shape of dose-related effects of CNS drugs. This further complicates dose finding and titraing the effective dose for human studies on basis of animal data. A final factor that should be considered is the animal itself. In most studies animals are used that are not raised in an enriched environment, as is the case in humans. A recent study shows that effects of a drug improved memory performance in standard housed but not in animals in an enriched environment. We need to better understand and control these different factors before we can improve translational models for cognition-enhancing drugs.

Biography:

Julian O’Kelly over the last fifteen years has worked in palliative care and neurorehabilitation as a music therapist, manager, educator and researcher. In addition to his research, he is a member in the expert panel regarding brain injuries at the "NHS National AHP Clinical Expert Database", an active participant in the "Society for Research Rehabilitation" and coordinator of the "Music Therapy Neurology Jiscmail Internet Forum", and is a regular active participant at international symposia and conferences. While working as a PhD Mobility Fellow at Aalborg University he published several peer-reviewed papers in the research area of his dissertation. The thesis examines the effects of music therapy on patients with impaired consciousness. The scientific papers gained considerable interest in the fields of health sciences and neuroscience leading to invitations to symposia in the US, Canada and throughout Europe in order to showcase his results. More recently, he has combined his fellowship with new roles as invited Associate Editor of a research topic with Frontiers in Human Neuroscience ‘Dialogues in music therapy and music neuroscience’, and Clinical Services Manager for Chroma, supporting the development of Arts Therapies across the UK.

Abstract:

Music therapists have been researching the effects of music therapy with those in coma, vegetative and minimally conscious states for over thirty years. There is a need for more standardised, evidence based approaches using concensus nomenclature, and greater dialogue with neuroscience in future work. This perspective has informed the development of a standardised assessment tool, the ‘Music Therapy Assessment Tool for Awareness in Disorders of Consciousness’ and a five year long research programme exploring the effects of music therapy in the assessment and rehabilitation for those with prolonged disorders of consciousness (PDOC), using behavioural and neurophysiological measures. Findings from the authors doctoral research will be presented alongside preliminary data from a cross-over study comparing the rehabilitative and prognostic potential of music therapy to preferred text narration, using a range of neurophysiological measures (EEG, heart rate variability, respiration) and video time sampled behavioral data. Findings will be discussed in relation to the complexity of the field of research, and the potential of music therapy as a tool for revealing what intact brain network activity exists in those with PDOC. Reflections will be provided on the relevance of these findings to the UK model of neuro-rehabilitation and the sustainability of music therapy in this competitive market.

Biography:

Mikhail A Lebedev is a senior research scientist at Duke University. He received a MSci from the Moscow Institute of Physics and Technology, Moscow in 1986 and a PhD from the University of Tennessee, Memphis in 1995. He worked at the Institute for the Problems of Information Transmission, Moscow, (1986–1991), the International School for Advanced Studies, Trieste (1995–1997) and the National Institute of Mental Health (1997–2002). His scientific interests include neurophysiology and brain–machine interfaces. He has authored more than 70 papers. He is also editor in several scientific journals.

Abstract:

Brain-machine interfaces (BMIs) hold promise to treat neurological disabilities by linking intact brain circuitry to assistive devices, such as robots that enact functionality of body parts. BMIs have experienced very rapid development in recent years, facilitated by advances in neural recordings, computer technologies and robotics. BMIs are commonly classified into three types: sensory, motor and bidirectional, which subserve motor, sensory and sensorimotor functions, respectively. Additionally, cognitive BMIs have emerged in the domain of higher brain functions. BMIs are also classified as noninvasive or invasive according to the degree of their interference with the biological tissue. Although noninvasive BMIs are safe and easy to implement, their information bandwidth is limited. Invasive BMIs hold promise to improve the bandwidth by utilizing multichannel recordings from ensembles of brain neurons. BMIs have a broad range of clinical goals, as well as the goal to enhance normal brain functions. Moreover, BMI technology in the future may be used to establish communication between individual brains.

Biography:

Ronald Swatzyna received his Master of Science and Doctorate of Philosophy from The University of Texas Arlington. Currently, he is the Director of Electro-Neurophysiology Research, Director of Neurotherapy at the Tarnow Center for Self-ManagementSM, and is an associate of Brain Science International. He is a Licensed Clinical Social Worker Supervisor, Board Certified in Neurotherapy and Biofeedback by the Biofeedback Certification International Alliance (BCIA). For 18 years, he has analyzed and treated the most diagnostically challenging cases in both inpatient and outpatient settings. As a Researcher, he has presented and/or published over 50 peer-reviewed papers on brain dysfunction, psychotropic medication and other related topics at national and international conferences and is a Special Editor for WebmedCentral plus and Clinical EEG and Neuroscience. In 2011, he was inducted into Sigma Xi: The Scientific Research Society: Rice University/Texas Medical Center Chapter and in 2013, he accepted an appointment to the Board of Directors. He is a Veteran of both Vietnam and the first Gulf War, and his personal battle with a traumatic brain injury and post-traumatic stress disorder has motivated him to become a leading expert in brain dysfunction.

Abstract:

Pharmaco-EEG studies using clinical Electroencephalograms (EEG) and quantitative EEG (qEEG) technologies have existed for over four decades. This is a promising area which could improve psychotropic intervention using neurological data. One of the objectives in our clinical practice has been to collect Electroencephalography (EEG) and quantitative EEG (qEEG) data. In the past five years, we have identified a subset of refractory cases (n=386) found to contain commonalities of a small number of electrophysiological features (neurobiomarkers) in the following diagnostic categories: mood, anxiety, autistic spectrum, and attention deficit disorders. Four neurobiomarkers were noted in the majority of medication failure cases and these abnormalities did not appear to significantly align with their diagnoses. Those were: encephalopathy, focal slowing, beta spindles, and transient discharges. To analyze the relationship noted, they were tested for association with the assigned diagnoses. Fisher’s Exact Test and Binary Logistics Regression found very little (6.25%) association between particular EEG/qEEG abnormalities and diagnoses. Findings from studies of this type suggest that EEG/qEEG provides individualized understanding of pharmacotherapy failures and has the potential to improve medication selection.

Biography:

Sam Greenblatt is a Technologist In Residence at Nano Global working nanotechnology’s impact worldwide. He focuses on manipulating properties and structures at the nanoscale in medicine. He also works on building Nano Global’s relationships with universities and startups. Sam is a consultant for technology companies to define strategies and offer technology services beyond the company’s business strategy. He creates strategic requirements for clients’ businesses by working with them to determine long-term technology-related decisions and create the appropriate operating model. Mr. Greenblatt is a Technologist in Residence at several technology companies where he uses his history of successfully helping companies bring technology to market. He helps the management team source and evaluate areas of growth. Sam served as CTO and General Manager of Engineering Solutions at Dell. He created strong alliances that developed a cross-line of business offerings for a cohesive architecture, making customers’ offerings run more efficiently. He is a recognized expert in Object Technology, IaaS, PaaS, and HPC (Red Hat OpenStack, Azure, HyperV, VMware). He built solutions based on Cloud, Analytics, Big Data, and Enterprise Applications (SAP and Oracle). He was the chief architect, and technologist at the Enterprise Solution Group involved in the architecture, communication and technical promotion of Dell’s Enterprise family of products. Sam has served on USDL (Linux Foundation) 4 years, Object Management Group (11 years), Eclipse Board (1 Year), and the DMTF Board (2 Years). He is the primary inventor on 4 US Patents in Object Technology. He was a CTO at Hewlett-Packard, Candle Corporation and Chief Innovation Officer at Computer Associates. Sam also was an adjunct professor of Computer Science at Temple University and LaSalle University.

Abstract:

Raman spectroscopy is the physicochemical technique for the rapid identification bacteria, viruses, and pathogens. The use of a portable Raman spectroscopy generates a Raman fingerprint from the surfaces using a microbial sample, to quantify information that can be used to characterized, discriminated and identify microorganisms. We use the coherent anti-Stokes Raman spectroscopy and will l discuss how a lower cost and speedy collection time will allow treatment of sufaces using to detect biolife and is remediation. In this talk we will show detection and remediation on skin and surfaces providesd by a groundbreaking advancement in managinghealth care environments. It is the world’s first and only multilayer defense system that offers instant disinfection and up to 24 hours of protection on skin and 14 days of protection on other relevant surfaces. The unique combined use of the Nano Pure technology on skin and surrounding surfaces offers an unmatched long-term, multilayer defense against the spread of unwanted microbes after detection. A complete solution.

Biography:

Gianni Colini - Baldeschi, MD was the Assistant Professor in the Department of Anesthesiology, S. Camillo-Forlanini Hospital, Rome, 1981. In 1995, he became the Director of the Pain Therapy Unit. In 1999, he took the position of Director of the Pain Therapy Unit at the San Giovanni – Addolorata Hospital in Rome where he works today. He is certified by the World Institute of Pain as a FIPP in 2008. He is the Secretary of the Italian Chapter of the International Neuromodulation Society in 2010, and later he took the position of President of the Italian Chapter in 2013.

Abstract:

This prospective observational study that took place over three years takes into account the metabolic parameters and capillaroscopy. The aim of our study is to identify the assessment of metabolic and dynamic capillaroscopy parameters thatmay be predictive of the outcome of SCS in patients affected with non-revascularizable chronic critical limb ischemia. Forty patients, 16 female and 24 male, average age 69±8, underwent microcirculatory screening with transcutaneous oximetry and dynamic capillaroscopy on the big toe nailfold; all patients were affected by chronic critical ischemia from atherosclerotic arterial disease, defined on the basis of the TransAtlantic Inter-Society Consensus criteria, and identified as non-revascularizable. Conservative treatment had proved to be of little or no effect. Follow-up visits were scheduled at three, six, and twelve months after implantation. The procedure was performed placing an Octrode (St. Jude Medical, St. Paul, MN, USA) on the dorsal columns of the spinal cord with the tip at T8-T9. Two groups were identified on the basis of transcutaneous oximetry measurements: group A (22 patients) and group B (18 patients), responding differently to the postural test. Patients affected by non-reconstructable chronic limb ischemia can benefit from SCS not only in terms of relief from their ischemic pain, but also of wound healing and limb salvage. Spinal neuromodulation is an effective therapy option in the management of patients affected by non-reconstructable chronic critical limb ischemia.

Biography:

Srikanth Ramaswamy is an in silico neuroscientist. He studies the principles of synaptic organization in a digital reconstruction of neocortical tissue. He graduated from the National Institute of Engineering in Mysore, India with a first class Honors degree n Electrical Engineering in 2002. In 2003, he was awarded a British Chevening Scholarship by the Foreign and Commonwealth Office, UK for a Master’s in Electrical Power Engineering at the University of Strathclyde in Glasgow, which he completed with commendable mention in 2004. During my Master's, he developed a keen interest in neuroscience and won a scholarship by the BBVA Foundation to work with Profs. Gonzalo de Polavieja and Pablo Varona at the Universidad Autonoma de Madrid between 2005 and 2006. In 2006, he joined the Blue Brain Project headed by Prof. Dr. Henry Markram at the EPFL in Lausanne as one of its first scientific team members and began working on my PhD thesis, which he completed in 2011. His thesis focused on modeling synaptic connections between neurons, and on validating the model against experimental data. Since 2011, he is a senior neuroscientist in the Blue Brain Project, where he leads efforts in modelling synaptic in a digital reconconstruction of neocortical tissue.

Abstract:

The Blue Brain Project has established a unifying data-driven process for the digital reconstruction of a prototypical neocortical microcircuit. The process unifies a vast body of anatomical and physiological data on ion channel kinetics and distributions, neuron morphologies and electrical types, synaptic kinetics and dynamics to yield an in silico reconstruction of the cellular and synaptic organization of juvenile rat somatosensory cortex. We present a draft anatomical and physiological map of a prototypical neocortical microcircuit. The map represents the first comprehensive integration of available data and knowledge in a quantitative in silico reconstruction of a part of the brain. To achieve this, a novel predictive strategy was developed using sparse data on the cellular and synaptic organization of the somatosensory cortex of a two-week old rat. The microcircuit is 0.29 mm3 in volume and contains about 31,000 neurons belonging to 55 morphological neuron types and 207 morpho-electrical sub-types distributed across 6 layers. The resulting reconstruction is broadly consistent with current knowledge about the neocortical microcircuit and provides an array of predictions on its structure and function across neuronal, synaptic, and circuit levels. The models in the reconstruction are available as a public resource for collaborative and iterative refinement, and in silico neuroscience.

Biography:

Shashi Ahuja is a Graduate from MAMC, New Delhi, India. She did her Master’s in Ophthalmology from SMS Medical College, Jaipur, India. Presently, she is working as an Associate Professor at JIPMER, India. She was awarded Shyam Lal Saksena Memorial Award, 2015 by National academy of Medical Sciences, India. She was also awarded CRISIL Medicall Innovation Healthcare award (Bronze) in 2012. Research work of PG student under her guidance was selected for AIOS-ARC Young Researcher’s Award, and ranked among the top twelve submissions, 2014. She has over seven international publications. She is a Member, Postgraduate Research Monitoring Committee at JIPMER, India and a Member, Editorial Board/Reviewer of various international journals. Currently, she is the Principal Investigator in two on-going projects. Presently, she is the guide for about 4 Postgraduates in Master of Ophthalmology.

Abstract:

Background: Papilledema is defined as an optic disc swelling that is secondary to elevated intracranial pressure. Early diagnosis of papilledema can help in early intervention thus preventing visual loss and even death. Optical Coherence Tomography (OCT) is a non-invasive imaging technique which can detect and quantify diffuse thickening of the Retinal Nerve Fiber Layer (RNFL) in eyes with optic disc edema. Objective: To assess the difference in the RNFL thickness in patients with papilledema from controls using OCT and to correlate the RNFL thickness with the degree of papilledema. Materials & Methods: All adult patients diagnosed or suspected to have papilledema were included in the study. Disc photographs were graded according to modified Frisen criteria. Fast RNFL protocol on time domain OCT was used. Cases and controls were compared. Results: A total of 100 cases and 126 controls were studied. Statistically significant thickening of Retinal Nerve Fibre Layer (RNFL) was seen in all quadrants in patients with papilledema as compared to controls. A positive correlation was found between Frisen grading of papilledema RNFL thickness measurements Conclusions: Thickening was mainly in the inferior and superior peripapillary region and was greater in higher grades of papilledema. A strong positive correlation was found between RNFL thickness and the Frisen scale for grading of papilledema. OCT can be included as a routine non-invasive quantitative tool for detection of early papilledema.

Biography:

Abstract:

We devised a method for comprehensive analysis of the flow of activity underlying the averaged EEG Event-Related Potentials (ERP). This method identifies the network of local activations sampled with multiple electrodes, their timing relative to the event and their frequency characteristics. Nevertheless we noted that the comprehensive analysis yields simple networks, which could be summarized as a superposition of two underlying processes, spread in space and time. These processes are seemingly perception and attention-related. However, due to its spread, the attention-related process could be sampled from just a single channel. Furthermore, due to the simplicity of the emerging envelope its correlates could also be sampled from single-trials analysis and fom continuous EEG in a manner, which is rather robust to noise. Such an effective and simple to use attention-related marker seems highly usable in the evaluation of treatment effect and in treatment direction for a plurality of neurological and psychiatric dysfunctions. We demonstrate the effectiveness and applicability of our attention marker in multiple fields including ADHD, migraine, depression, dementia, neural rehabilitation and aneshtesia.

Biography:

Keqiang Ye received his PhD from Emory University in 1998 and Postdoctoral training at Johns Hopkins University in 2001. He is a Full Professor in Department of Pathology and Laboratory Medicine, Emory University and has published over 140 papers in top tier journals. He also serves as Editorial Board Member for several reputed journals.

Abstract:

Asparagine Endopeptidase (AEP) is implicated in various human disorders including cancers and neurodegenerative diseases. AEP is upregulated and activated in normally aged brain and human Alzheimer’s Disease (AD) brain, and plays a critical role in mediating the pathophysiology of AD. Here we report an orally bioactive and brain permeable AEP inhibitor that blocks the cleavage of tau and APP, and alleviates the cognitive deficits in mouse models of AD. We performed a high-throughput screen and discovered several compound families with potent inhibitory activity. After analyzing the druglikeness properties of the compounds, we identified a nontoxic and selective AEP inhibitor family, termed compound 11, that selectively blocks AEP but not other related cysteine proteases. Strikingly, co-crystal structure analysis revealed a dual active site-directed and allosteric inhibition mode of this compound class. Chronic treatment of tau P301S and 5XFAD transgenic mice with oral administration of the inhibitor reduces tau and APP cleavage, ameliorates synapse loss and augments Long-Term Potentiation (LTP), resulting in protection of memory. Therefore, these findings demonstrate that this AEP inhibitor may be an effective clinical therapeutic agent towards AD.

Biography:

Bazhanova Elena has completed her PhD in 1997 from Astrakhan State Medical Institute, Astrakhan, Russia and Post-doctoral studies from Sechenov Institute of Evolutionary Physiology and Biochemistry, St-Petersburg, Russia. She is the Leading Researcher, Laboratory of Comparative Biochemistry of Cell Functions, Sechenov Institute of Evolutionary Physiology and Biochemistry, Russia. She studies mechanisms of neuron apoptosis regulation in aging, using some pharmacological approaches. She has published more than 35 papers in reputed journals. She is a Regular Reviewer in Russian Journal of Physiology.

Abstract:

Age-dependent loss of brain neurons leads to declining cognitive abilities, behavior changing. Actual issue is to provide a new therapeutic strategy for treatment of aging neurodegeneration. Aims of investigation were to study mechanism of neuronal apoptosis in sensorimotor cortex in physiological and pathological aging, and to investigate role of exogenous neurometabolites (angiogen, cytoflavin, piracetam) in regulation of apoptosis and cortex functions in aging. We used HER2/neu transgenic mice, wild-type FVB/N line. We determined apoptosis level and CD95, caspase-8, caspase-3, p53, Bcl-2, Mcl-1, Erk1/2 expression (TUNEL, immunohistochemistry, Western blotting), and psycho-emotional and locomotor status of mice. Locomotor activity decreased and anxiety increased in aged FVB/N, which correlates with the high level of apoptosis. Locomotor activity of HER2/neu is low, and does not change with aging. Apoptosis level is low in this line of mice, and is stable in aging. Cause of it is overexpression of HER2 tyrosine kinase receptor, which supresses p53-dependent pathway. Angiogen, cytoflavin, piracetam have a marked neuroprotective effect on cortex neurons of FVB/N, HER2/neu aged mice. These drugs improved locomotion and psychological status in both mouse strains. The involvement of these drugs in apoptosis regulation depends on biochemical neuron status, which is determined by genetic line. HER2 overexpression alters course of biochemical processes and signaling in cells. Studied neurometabolites have moderate stimulation of apoptosis by extrinsic and p53-dependent pathways in HER2/neu mice. It has clinic significance, because low apoptosis leads to high carcinogenesis. These drugs decrease significant age-dependent apoptosis in wild-type old animals, and this way prevent neurodegeneration.

Biography:

Beatrice Arosio is a graduate with honours in 1989 and PhD in Physiopathology of Aging in 1997 at the University of Milan (UNIMI). Since 2001, she is a Researcher and Director of the Laboratory of the Geriatric Unit at UNIMI. In 2014 and 2015, she was selected as Reviewer by the European Commission Research Executive Agency (Horizon 2020 program) and by the Executive Government Agency of National Science Centre. She is a member of Gerontological Society of America and Italian Society of Geriatric and Gerontology. She is a Senior Editor of “Journal of Alzheimer’s Disease” and referee for international journals. She is an author of 100 papers and 150 contributions to conferences.

Abstract:

In late-onset Alzheimer’s disease (AD) the probability of finding other abnormalities in addition to amyloid-beta (Aβ) and tau deposition is increased. The changes induced by aging may be concauses of AD onset and progression. Inflammation, involved in neurodegeneration, can accelerate telomere shortening that reflects cellular turnover and exposure to oxidative and inflammatory damage. IL-10 affects neuronal homeostasis and inhibition of Aβ-induced generation of IL-6, Tumor Necrosis Factor-α (TNF-α) and Interferon-γ (IF-γ). After a follow-up period of two years, we have categorized 31 elderly AD as slow (ADS) or fast (ADF) on basis of Mini-Mental State Examination (MMSE) decline (≤3 or ≥5 points, respectively). In peripheral blood mononuclear cells from AD and 20 age-matched controls (HC), we have evaluated IL-10 and IL-6 production after Aβ stimulation, telomere length (TL) and polymorphisms in the promoter of IL-10, IL-6, TNF-α, IF-γ and Transforming Growth Factor-β1. Antigen-specific IL-10 production was higher in ADS and HC after stimulation compared to resting production (40.7±13.7 versus 59.0±27.0; 47.1±25.4 versus 55.3±27.9, respectively; p<0.05) and abrogated in ADF in which prevails AA IFN-γ low-producing genotype (39.7±14.4 versus 42.2±22.4). MMSE decline correlated with TL (R2=0.284; p=0.008) and ADS displayed shorter telomeres compared to ADF and HC (2.0±0.4, 2.5±0.4, 2.3±0.4, respectively; p=0.034). ADF inability to mount anti-inflammatory response to Aβ contributes to deregulation of immune and replicative responses responsible of longer telomeres. These factors might predict the AD progression rate.

Biography:

Urszula Wojda, PhD, DSc/Habil, Full Professor of Biological Sciences, a Head of Laboratory of Advances Preclinical Research (LaPrec) at the Nencki Institute awarded by EU Commission with ‘HR Excellence in Research’. She completed PhD studies in the Nencki Institute and training in the Pasteur Institute in France, and postdoctoral studies at the NIH, USA (1996-2002). She has been serving as an Editorial Board Member as an Polish expert at the Management Board of the EU Joint Programming for combating Neurodegenerative Diseases (JPND). She has published more than 30 papers in reputed journals.

Abstract:

Alzheimer’s disease (AD) is a progressive, irreversible neurodegenerative disorder and the most common age-related dementia affecting over 44.4 million people worldwide. With the demographic shift towards aging societies, this number is expected to double every 20 years, what generates an overwhelming socioeconomic burden on society. Before the onset of clinical symptoms, AD develops for tens of years in the preclinical phase and mounting evidence indicates that the effectiveness of therapeutic modalities critically depends on the early diagnosis of AD. Unfortunately, no preclinical diagnostic methods exist and available treatments for AD are only symptomatic. It becomes clear that progress in AD therapy and diagnostics relies to a great extent on elucidation of early molecular AD pathomechanisms, and the identification of novel drug targets and biomarkers of early AD, preferably in easily available diagnostic materials, such as blood. Indeed, in AD some early molecular changes are observed in peripheral cells, such as blood lymphocytes. These include changes in the level of oxidative stress markers and aberrant cell cycle regulation. These findings provide support for the oxidative stress and cell cycle hypotheses of AD pathogenesis and open perspectives for the application of easily accessible blood lymphocytes for the development of new diagnostic methodologies involving early AD biomarkers in lymphocytes.

Biography:

Hossein Pakdaman graduated in Neurology from the Pennsylvania and Henry Ford University (1976). He is Professor of Neurology affiliated to Shahid Beheshti University School of Medicine (since 1990), President of Iranian Neurological Association (since 1991), Director of Iranian Neurological Board Examination (since 1978). Also, he has published more than 40 papers in international journals and is Chairman of Iranian Journal of Neurology (since 1998).

Abstract:

MLC601 is a possible modulator of amyloid precursor protein processing, and in a clinical trial study MLC601 showed some effectiveness in cognitive function in Alzheimer's disease (AD) patients. We aimed to evaluate the effectiveness and safety of MLC601 in the treatment of mild to moderate AD as compared to 3 approved cholinesterase inhibitors (ChEIs) including donepezil, rivastigmine and galantamine. In a multicenter, non-blinded, randomized controlled trial, 264 volunteers with AD were randomly divided into 4 groups of 66; groups 1, 2, 3 and 4 received donepezil, rivastigmine, MLC601 and galantamine, respectively. Subjects underwent a clinical diagnostic interview and a cognitive/functional battery including the Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale – Cognitive subscale (ADAS-Cog). Patients were visited every 4 months, and the score of cognition was recorded by the neurologists. There were no significant differences in age, sex, marital status and baseline score of cognition among the 4 groups. In total, 39 patients (14.7%) left the study. Trend of cognition changes based on the modifications over the time for MMSE and ADAS-cog scores did not differ significantly among groups (p = 0.92 for MMSE and p = 0.87 for ADAS-Cog). MLC601 has shown a promising safety profile and also efficacy compared to the 3 FDA-approved ChEIs donepezil, rivastigmine and galantamine. There is a need to conduct more randomized controlled trials with a combination of MLC601 and ChEIs to find out whether MLC601 may provide additional cognitive and/or functional benefits in AD when combined with ‘first-line’ treatments.

Biography:

Telma Quintela obtained her BSc in Biology in the University of Coimbra in 2004, and in 2010 she obtained the PhD in Biomedicine in the University of Beira Interior. She is currently a Post-doctoral researcher at the University of Beira Interior and the main objective of her research includes understanding how choroid plexus influences the circadian rhythm cellular mechanisms and how these can be altered in Alzheimer´s disease.

Abstract:

The suprachiasmatic nucleus (SCN) of the mammalian hypothalamus is considered the master circadian pacemaker. The SCN clockwork is a cell autonomous mechanism consisting of a series of interlocked transcriptional/ post-translational feedback loops. However, the SCN is not the only structure in the brain displaying daily rhythms. Recently it was demonstrated that choroid plexus (CP) expresses core clock genes that are subjected to circadian regulation in a gender dependent manner, suggesting that hormones can regulate circadian rhythmicity in CP. Moreover, using CP explants cultured from mice carrying the Period-luciferase transgene, we report that CP exhibits endogenous circadian rhythms of PERIOD2::LUCIFERASE expression. We also observed that estrogen depletion following ovariectomy affects the CP circadian rhythmicity and that Period 1 and 2 mRNA expression are up-regulated by estradiol (E2) in rat CP epithelial cell cultures. In addition, the mechanism underlying these responses was investigated, and we provide evidence that the estrogen receptor is involved. Therefore, our study reinforces the importance of estrogens on circadian oscillators and supports the hypothesis that E2 directly controls the molecular clock machinery present in the CP.

Biography:

Asok Kumar Mukhopadhyay, MD, is a Professor and Head of the Department of Laboratory Medicine of India’s Premier Medical Institute, AIIMS since 2006. His research interest is in neurodegenerative disorders like Alzheimer’s disease, vascular dementia and Parkinson’s disease, psychoneuroimmunology and molecular psychiatry like depression and stress, and in out-of the paradigm work in concept building and developing theories on consciousness studies. His valuable published papers could be accessed from AIIMS, Department of Laboratory Medicine website.

Abstract:

While doing genetic polymorphism study on 80 patients of Alzheimer disease (AD) and 50 cases of Vascular dementia (VaD) recruited from cognitive disorder clinic of All India Institute of medical sciences, it was noticed that the phenomenon of gene-gene interaction or epistasis, when genes are in some specific combination, has been altering the odds ratio of having disease. This was a cross sectional, observational study with 120 controls of comparable gender and age. Polymorphism of five genes, namely ApoE genes, MTHFR-C677T, MTHFR-A1298C, IL-6 174 G/C and PON1 genes, were studied and their epistatic interactions were examined. Besides the single gene’s influence on alteration of odds ratio, it was observed that specific combination of (presence or absence) of MTHFR 677 and IL-6-174 genes, MTHFR 1298 and IL-6-174 genes, PON1 rs854560 and ApoE €4 genes , PON1 rs662 and ApoE €4 genes have been significantly altering the odds ratio of having AD, VaD or both. No epistatic interaction was observed between MTHFR677 and MTHFR 1298 genes. Since the genes like ApoE and PON1 are on different chromosomes (chromosome 19 and chromosome 7 respectively) and MTHFR and IL-6174 genes are also on different chromosomes (chromosome 1 and chromosome 7 respectively), it is of great concern how the genes which are at such a distance apart interact with each other to influence the phenotypic outcome in form of AD or VaD. These preliminary findings in Indian population attending a tertiary care hospital are stimulus for further investigating the mechanism of gene-gene interaction or epistasis.

Biography:

Sholpan Askarova received a Degree of the Candidate of Biological Sciences from Al-Farabi Kazakh National University in 2014 and a PhD degree in Biological Engineering from University of Missouri in 2011. She also has completed Postdoctoral studies from McGowan Institute for Regenerative Medicine, University of Pittsburgh. She is the Head of the Laboratory of Bioengineering and Regenerative Medicine, Center for Life Sciences, Nazarbayev University. Her current work focuses on the role of membrane biophysics and related cell signaling pathways in neurodegenerative diseases such as Alzheimer’s disease, and cell therapeutic approaches for the treatment of chronic conditions.

Abstract:

There is an increasing body of evidence that Blood-Brain Barrier (BBB) dysfunctions contribute significantly to the development and progression of Alzheimer’s Disease (AD). Since Cerebral Endothelial Cells (CECs) are the main cell components of the BBB, we studied the effects of Amyloid β peptide oligomers (Aβ42) on the adhesion mechanisms of cerebral endothelium and role of the Receptor for Advanced Glycation End-Products (RAGE) and Reactive Oxygen Species (ROS) in Aβ mediated cell toxicity and downstream cell signalin pathways in CECs. Increased deposition of amyloid β peptide in cerebral vasculature and enhanced transmigration of monocytes across the BBB are frequently observed in AD brains. Since rolling adhesion is the initial step in the transmigration of monocytes and is governed by dynamic bond formation and rupture between selectins and Sialyl LewisX (sLex), we applied Atomic Force Microscopy (AFM) with cantilever tips bio-functionalized by sLex to examine the effects of Aβ42 on the sLex-selectin adhesion at the surface of CECs and demonstrated that A42 increases the probability of cell adhesion to sLex-coated cantilevers and cell elasticity, and that effects can be counteracted by statin. We also report that Aβ42 promotes expression of P- selectin and increases actin polymerization, and these events are correlated with elevated Reactive Oxygen Species (ROS) production. There is evidence that Aβ mediate oxidative damage to CECs and and trigger the downstream MAPK/ERK pathway. Still, the cell surface binding site for Aβ42 and exact sequence of these events have yet to be elucidated. In this study, the Receptor for Advanced Glycation End-Products (RAGE) was postulated to function as a signal transducing cell surface receptor for Aβ42 to induce Reactive Oxygen Species (ROS) generation from NADPH oxidase and trigger downstream pathways for the phosphorylation of extracellular signal-regulated kinases (ERK1/2) and cytosolic phospholipase A2 (cPLA2). We found that Aβ42 competed with the anti-RAGE antibody (AbRAGE) to bind to RAGE on the surfaces of CECs. In addition, AbRAGE abrogate Aβ42-induced ROS production and the colocalization between the cytosolic (p47-phox) and membrane (gp91-phox) subunits of NADPH oxidase. AbRAGE as well as NADPH oxidase inhibitor and ROS scavenger suppressed Aβ42 -induced ERK1/2 and cPLA2 phosphorylation in CECs. Our findings demonstrating an effect of Aβ42 oligomers on CECs selectin adhesion and the role of Aβ-RAGE interaction in BBB dysfunctions provide insights into the mechanism of inflammation in AD brains and may offer new approaches for prevention and treatment of the disease.

Biography:

He has completed his PhD in “Experimental Medicine” School of Medicine University of Messina in 1999. Now, he is Full Professor in Pharmacology at the University of Messina. He won many awards such as Gionco Prize and Galeno Prize. He has published more than 500 papers in International journals. He attended a lot of talks in many national and international meetings.

Abstract:

Oxidative stress is central in Parkinson's disease (PD) and nuclear transcription factor related to NF-E2 (Nrf-2) is involved in neuroprotection against PD. The aim of the present study was to investigate the neurotherapeutic action, Nrf-2 dependent, of DMF in a mouse model of PD. Mice received four injections of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Starting 24 h after the first administration of MPTP, animals were treated with DMF (10, 30 and 100 mg/kg, by oral gavage) daily for 7 days and, on the 8th day mice were subjected to behavioural test. Results: DMF treatment significantly reduced neuronal degeneration of dopaminergic tract and behavioral impairments induced by MPTP administration. Moreover, treatment with DMF prevented dopamine depletion increasing tyrosine hydroxylase (TH) and dopamine transporter (DAT) and also reduced α-synuclein-positive neurons. Furthermore, DMF treatment up-regulated Nrf-2 pathway, increasing NeuN+/Nrf-2+ cells in the striatum and inducing activation of manganese superoxide dismutase (Mn-SOD) and heme-oxygenase-1 (HO-1). Also, DMF reduced ciclo oxygenase 2 (COX-2), lowered nitrotyrosine (NT) and neuronal nitrite oxide synthase (nNOS) expression, restored nerve growth factor (NGF) levels and preserved by microtubule-associated protein 2 (MAP-2) alterations. We conclude that the relevance of our findings is underlined in that the DMF, as Nrf-2 based therapies, offers a novel cytoprotective modality that further augments the natural antioxidant response in neuronal environment and is extended to other neurodegenerative and inflammatory disease models.

Biography:

Ivanova E A received her PhD from Yaroslavl State Medical Academy and undertook Postdoctoral studies at the laboratory of psychopharmacology, Zakusov Institute of Pharmacology. She is a senior researcher of the laboratory of psychopharmacology, Zakusov Institute of Pharmacology. She has published more than 15 papers in peer-reviewed journals and co-authored 3 patents RUS.

Abstract:

Today neuroinflammation is considered a response of the CNS not only to acute brain damage, but also to neurodegeneration. While early inflammation as a reaction to damage is directed to the activation of neuroprotection, a transition to chronic neuroinflammation is harmful for the CNS. Nowadays attention is being increasingly focused on the role of protein-degrading enzymes in inflammation. The activity of prolylendopeptidase enzyme (PREP) is known to change in both inflammation and neurodegeneration. Dipeptidyl peptidase IV (adenosine deaminase (ADA) binding protein, DPP-4) and related peptidases hydrolyze cytokines, neuropeptides and immunopeptides. In our laboratory the activity of PREP, DPP-4 and ADA was measured in plasma and cerebrospinal fluid (CSF) of outbred rats with experimental Parkinson’s disease (PD). Enzyme activity assessment demonstrates that the activities of peptide (DPP-4, PREP) and purine metabolism (ADA) enzymes were altered in rats with PD induced by 6-hydroxydopamine (6-OHDA) injection in the left medial forebrain bundle and by intraperitoneal subchronical administration of rotenone. PREP activity increased in the plasma and DPP-4 activity increased in the CSF of rats with rotenone-induced PD. Rats with a more severe PD induced by 6-OHDA had increased activity of DPP-4 in plasma and decreased activity of DPP-4 and PREP in the CSF. Reduced ADA activity in plasma was demonstrated in both models of PD. In summary, the results demonstrate that the activity of peptide and purine metabolism enzymes is altered in both PD models and these changes can be considered a non-specific marker of neuroinflammation and a possible target of neuroprotective drugs.

Biography:

Ivanova E A received her PhD from Yaroslavl State Medical Academy and undertook Postdoctoral studies at the laboratory of psychopharmacology, Zakusov Institute of Pharmacology. She is a senior researcher of the laboratory of psychopharmacology, Zakusov Institute of Pharmacology. She has published more than 15 papers in peer-reviewed journals and co-authored 3 patents RUS.

Abstract:

Today neuroinflammation is considered a response of the CNS not only to acute brain damage, but also to neurodegeneration. While early inflammation as a reaction to damage is directed to the activation of neuroprotection, a transition to chronic neuroinflammation is harmful for the CNS. Nowadays attention is being increasingly focused on the role of protein-degrading enzymes in inflammation. The activity of prolylendopeptidase enzyme (PREP) is known to change in both inflammation and neurodegeneration. Dipeptidyl peptidase IV (adenosine deaminase (ADA) binding protein, DPP-4) and related peptidases hydrolyze cytokines, neuropeptides and immunopeptides. In our laboratory the activity of PREP, DPP-4 and ADA was measured in plasma and cerebrospinal fluid (CSF) of outbred rats with experimental Parkinson’s disease (PD). Enzyme activity assessment demonstrates that the activities of peptide (DPP-4, PREP) and purine metabolism (ADA) enzymes were altered in rats with PD induced by 6-hydroxydopamine (6-OHDA) injection in the left medial forebrain bundle and by intraperitoneal subchronical administration of rotenone. PREP activity increased in the plasma and DPP-4 activity increased in the CSF of rats with rotenone-induced PD. Rats with a more severe PD induced by 6-OHDA had increased activity of DPP-4 in plasma and decreased activity of DPP-4 and PREP in the CSF. Reduced ADA activity in plasma was demonstrated in both models of PD. In summary, the results demonstrate that the activity of peptide and purine metabolism enzymes is altered in both PD models and these changes can be considered a non-specific marker of neuroinflammation and a possible target of neuroprotective drugs.

Biography:

Eelke Snoeren has completed her PhD from the Utrecht University in The Netherlands and Post-doctoral studies from the the Arctic University of Norway. She now works as an Associate Professor in the Department of Psychology at the Arctic University of Norway. She has published 19 papers in reputed journals and 1 book chapter. She has taken part in several commissions of trust. She is elected member of the Norwegian Neuroscience Society Council in Norway, and was invited to the scientific advisory boards of the International Society of Sexual Medicine (ISSM) and the European Society for Sexual Medicine (ESSM).

Abstract:

This study investigated the role of estrogen receptors alpha (ERα) in the ventromedial nucleus of the hypothalamus (VMN),the preoptic area (POA), the medial amygdala (MePD) and the bed nucleus of stria terminalis (BNST) in sociosexual behavior in female rats. We used a short hairpin ribonucleic acid (shRNA) encoded within an adeno-associated viral (AAV) vector directed against the ERα gene to reduce the number of ERα in the VMN or POA, or in BNST or MePD in female rats. The rats were housed in groups of four ovariectomized females and three males in a seminatural environment for 8 days. In comparison to traditional test set-ups, the seminatural environment provides an arena in which the rats can express their full behavioral repertoire, which allowed us to investigate multiple aspects of social and sexual behavior in groups of rats. A reduction of ERα expression in the VMN or POA diminished the display of paracopulatory behaviors and lordosis responses compared to controls, while the lordosis quotient remained unaffected. This suggests that ERα in the VMN and POA play an important role in intrinsic sexual motivation. The reduction in ERα did not affect the social behavior of the females, but the males sniffed and pursued the females with reduced ERα less than the controls. This suggests that the ERα in the VMN and POA is involved in the regulation of sexual attractiveness of females. The ERα in the MePD and BNST, on the other hand, plays no role in sociosexual behavior.

Biography:

Peter A Serrano received his Undergraduate degree from UCLA and his Doctorate in Biopsychology from the University of California, Berkeley. Following in the footsteps of his graduate mentors, Prof. Mark Rosenzweig (Psychology) and Prof. Edward Bennett (Biochemistry), he continues to merge these two disciplines (Psychology and Biochemistry) in his research. His current interest involves how the trafficking of PKMζ during episodes of memory is disrupted with methamphetamine treatment. His hypotheses revolve around the role of inflammation involving the upregulation of cycloxygenase-2 (COX-2). As this protein can impair the ubiquitin proteosome pathway, altering the trafficking and protein turn over of PKMζ.

Abstract:

We evaluated the effects of methamphetamine on spatial learning and memory using the hippocampal dependent task, the radial 8-arm maze (RAM). Hippocampus was analyzed for synaptic markers important for memory and synaptic plasticity including the D1 receptor, the atypical protein kinase M zeta (PKM), and the AMPA receptor subunit GluA2. PKM is important for trafficking the GluA2 subunit to the membrane. Maintaining GluA2 on the synaptic membrane improves memory retention. We hypothesize that neuroinflammation plays a role in exacerbating the negative effects of MA-induced learning and memory deficits. One inflammatory marker in particular, cyclooxygenase-2 (COX 2) catalyzes the conversion of arachidonic acid into prostaglandins. Several prostaglandins are catalyzed by COX2, but one in particular is very toxic, the prostaglandin J2 (PGJ2). Thus, we are interested in determining how MA toxicity may activate this inflammatory pathway, perpetuating the toxicity leading to sustained cognitive deficits. Our results show MA produces deficits in learning the RAM after 6 weeks of abstinence. This was correlated with a decrease in PKM and D1 expression and increase in COX-2, PGJ2 and ubiquinated protiens. Additionally, bolus doses of MA (once per week for 3 weeks) after completing RAM training, results in memory retrieval deficits. Analyses of the hippocampus shows increased microglia expression and impaired trafficking of GluA2 in hippocampal area CA3. These data show that short-term acute binge doses of MA followed by long-term abstinence produce chronic inflammation that disrupts trafficking of synaptic markers that may exacerbate and/or sustain the long-term spatial memory deficits induced by MA.

Biography:

M Bruce MacIver completed his PhD in 1987 from the University of Calgary and went on to Postdoctoral studies at Stanford University School of Medicine. He started on the Medical School Faculty at Stanford in 1991 and was promoted to Full Professor in 2010. He directs the Neuropharmacology Laboratory at the Stanford Medical School and is affiliated with the Bioengineering, Bio-X and Neurosciences programs at Stanford University. He has published more than 60 peer-reviewed papers in reputed journals and has been serving as a Reviewer and Editorial Board Member of several journals for many years

Abstract:

Anesthetics are known to depress synaptic transmission, and this effect is thought to underlie the uncoupling of brain regions seen with cortical EEG recordings. We tested the hypothesis that anesthetic-induced depression of synapses leads to uncoupling of electrical activity between frontal cortex and hippocampus. The present study used electrophysiologically-guided electrode implants to record Schaffer-collateral to CA1 neuron mono-synaptic responses, as well as frontal cortical micro-EEG signals. Rats were allowed to recover from surgery and then isoflurane effects were characterized after several days (>7) to several months (<7) later. Simultaneous recordings of cortical and hippocampal micro-EEG signals, evoked synaptic responses, anesthetic concentration, vital signs and behavior were made. Loss of consciousness, measured as righting reflex, was consistently associated with increased synchronized delta activity, in hippocampus and cortex, as well as a novel ~15 Hz rhythmic oscillation produced by isoflurane in hippocampal micro-EEG recordings. Surgical anesthesia, measured as loss of tail-clamp reflex, was observed on the transition to burst-suppression activity in both hippocampal and cortical micro-EEG signals. Isoflurane produced a concentration-dependent depression of mono-synaptic responses: at surgical anesthetic depths, excitatory postsynaptic potentials were depressed by 26.6±4.2 % (n=5; p<0.001) of control amplitudes, but surprisingly, coupling between cortex and hippocampus was further enhanced. Clearly, our hypothesis was wrong, since increased coupling between brain regions was observed at the same time that mono-synaptic responses were depressed. We demonstrate for the first time that cortical-hippocampal coupling is increased at both low (loss of consciousness) and at high surgical concentrations of isoflurane.

Biography:

Pedro M R Reis has completed his PhD in Exercise Neuroscience in which he contributed for the develop methods for measureing and anlysing EEG during motion. These include the acurate detection of EEG electrodes and bases for Pharmaco-Mobile Body/Brain Imaging. He is a Research Scientist at the University of Erlangen, Germany.

Abstract:

Methodology that would allow the investigation of interactions between brain activity sources, natural motor behavior and drug interactions, would bring benefits such has personalised treatments for ADHD, and understanding of disease mechanisms. With such methods, investigators and clinicians would be able to monitor and adjust treatments of impairing motor conditions. On one hand, Pharmaco-EEG allow the inspection effects of substances in the central nervous system activity. However, Pharmaco-EEG leaves out the effects on motor behaviour and how physical exercise influences pharmacokinetics. On the other hand, electroencephalography suffers from inherited methodological problems that restrict its use during motion. Yet, this is the only light enough mobile noninvasive sensing modality with adequate temporal resolution to record brain activity on the time dimension of natural motor behaviour. Recent andvances allow for synchnous measurements of brain and body dynamics (MoBi). Combining MoBi methods with pharmacokinetic analysis results in the creation of Pharmaco-Mobile Brain Body Imaging (P-MoBi). Using source localisation to determine the cortex areas responsible for different activities, and the time resolution of the EEG for functional connectivity brain mapping, researchers may be abele to determine the changes and influences of the resulting interaction betewen exercise and medicaments on brain functions and corresponding motor performance. This talk presents the reseearch potential of P-MoBi methodologies and innovations that allow such measurements.

Biography:

Marcello Finardi Peixoto is Doctor of Medicine (MD) since 2001 and Master in Science (MsC). He is specialized in psychiatry since 2005. He have experience in the area of medicine, with an emphasis in psychiatry, internal medicine, sleep medicine, psychossomatics and nephrology acting on the following topics: depression, anxiety, sleep and hypertension. He work in his private practice in São Paulo, Brazil since 2003.

Abstract:

Objective: To observe the influence of the treatment of depression on the regularization of blood pressure and heart rate of individuals with hypertension and depression. Methods: A total of 30 individuals who were being treated for hypertension were diagnosed for depression participated in this study. Escitalopram (10 - 20 mg) was administered to 15 individuals, while the other 15 received placebo. These individuals were followed for 8 weeks with regular monitoring of blood pressure and heart rate. Scores on the Hamilton Depression Rating Scale were evaluated within the first, second, fourth, and eighth weeks of the study onset. The same 30 individuals were further divided into groups who had or had not undergone depression remission, regardless of whether the individual was receiving the active drug or placebo. Likewise, in order to observe the influence of sleep regularization, the patients were divided into groups based on whether their sleep quality had improved. Results: There was a significant decrease in the average systolic blood pressure of the normal-sleep group (−20.07±13.45 vs. −9.43±14.87 mmHg, p=0.04). Heart rate was lower in the escitalopram than in the placebo group: 66.88±9.62 vs. 74.19±9.55 bpm, p=0.04. Conclusion: Treatment with escitalopram decreased heart rate, improved sleep quality, and decreased blood pressure.

Biography:

Marcela Henríquez-Henríquez completed her MD, PhD and clinical specialization in Laboratory Medicine at Pontificia Universidad Católica de Chile and realized her Post-doctoral studies in Columbia University Institute of Human Nutrition. Currently, she works as Assistant Professor and Director of R&D in the Department of Clinical Laboratories of the School of Medicine, Pontificia Universidad Católica de Chile. Her research explores behavioral and molecular markers/endophenotypes for ADHD as tools to approach pathogenic mechanisms. Her results have been published in several journals including Frontiers in Neuroscience and Journal of Attention Disorders and were recently awarded in EB 2015 and the 5th ADHD World Congress.

Abstract:

In 1972, Gottesman and Shield introduced the concept of “endophenotypes” in behavioral genetics as a response to the pressing need for a construct able to bridge the explanatory gap in the genes-to-behavior pathway. They conceived endophenotypes as markers of genetic liability that lie in-between the gene and the clinical disorder. In being more proximal to primary gene products, they would have a less complex genetic architecture and allow for an easier identification of the genetic factors underling pathology. Additionally, endophenotypes would aid to elucidate the specific domains of brain function influenced by genetic risk variants. Intra-individual variability (moment to moment fluctuations in task performance) has been suggested as candidate endophenotype for ADHD. Traditional approaches to estimate intra-individual variability collapse responses across the entire task. Alternatively, more accurate statistics approaches like ex-gaussian and FFT analysis and mixed effect models allow for a better phenomenological description of moment-to-moment fluctuations in performance. Using a highly demanding Go-NoGo task and mixed-model analysis, we found that carriers of at least one copy of 2R or 7R-DRD4 alleles present faster deterioration in performance, independently of ADHD status. Ex-Gaussian analysis, on the other hand, allowed us to identify a geneX diagnosis interaction for the same allelic variants on the tau component of the ex-Gaussian distribution of response times, suggesting that attentional lapses (accepted phenomenological correlate for tau component in this case) may be predominantly expressed in ADHD patients carrying 2R or 7R-DRD4 alleles. Both approaches allowed us to unravel net genotype effects previously masked by traditional non-dynamic analysis.

Biography:

Ana Claudia Nunciato graduated in Physiotherapy from the University Center of Araraquara (2005). She is specialized in Exercise Physiology (2007) and Master in Physiological Sciences with emphasis Behavior Neuroscience by the Federal University of São Carlos - UFSCar (2011). Her PhD was by the Program of Graduate Studies in Biological Sciences (Physiology) with emphasis on Neuroscience Cellular and Molecular by the Institute of Biophysics Carlos Chagas Filho by the Federal University of Rio de Janeiro - UFRJ (2015). She is currently a Lecturer and Internship Supervisor in Neurological Physiotherapy area of the University Center of Araraquara (UNIARA).

Abstract:

This interface can be understood and explained from the relationship between cause and consequence, the relationship between sign, symptom, diagnosis or treatment. Thus, the objective is to correlate symptoms presented by neurological patients with a diagnosis of major depression and physical therapy. Depression is a disorder most common mood characterized by sadness, loss of interest or pleasure, feelings of guilt or low self-esteem, sleep or appetite disturbances, feeling of tiredness or fatigue and lack of concentration. A neurological disease affecting nearly 17% of the world population or 340 million people and it is estimated that in 2020 is the 2nd cause of disability according to WHO is considered. Several hypotheses have tried to explain the cause and onset of symptoms. It has been valuable in the development of conventional antidepressants that are thought to act by reversing these dysfunctional states of depression. The depression is comorbidity is present in neurodegenerative disease and in systemic diseases. All the pathologies share the same dysfunction and neurochemical changes in the central nervous system such as serotonergic hypofunction. Thus, in addition to the beneficial effects of antidepressants, the physical therapy through physical activity can stimulate neuroplasticity (synaptogenesis, enhanced glucose utilization, angiogenesis, and neurogenesis), improves psychological (social interaction) and physiological (monoamines and endorphins). The exercise and the antidepressant treatment are shown to have a strong reinforcing effect on adult neurogenesis. Therefore, the exercise and the physical therapy may be source non-pharmacology of improvement of depression.

Biography:

Abstract:

Of the various behavioral issues involved in mood disorders, decisional conflicts are of special importance. Neural circuitry involved in the decision-making process and social emotion involves the same circuits as major depression. The aim of this study was to investigate the decision making process in risk/reward situations in addition to moral conflict in depressed patients, using neuropsycho-physiological methods. Methods: Forty patients were studied, 20 with depression and 20 without. After had applied the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) and Hamilton Depression scale (HAM-D), the Iowa Gambling Task (IGT) and moral dilemmas were applied to analyze the decision-making behavior. The Skin Response (SCR) was recorded to examine the emotional arousal. Besides, an EEG was conducted to measure the Frontal Alpha Asymmetry Index (FAAI) and the sLORETA to identify cortical areas. Results: Depressed patients presented a lower net score (p<0.03) and poor emotional learning response. Furthermore, the FAAI and sLORETA study revealed more right activation in the neural circuits involved in the social and decision-making process in different frequencies bands. Conclusion: People with major depression have a dysfunction in the circuits that modulate cognitive, emotional and social behavior, and also, impairment in cognitive fluidity for evaluating strategies for risk-reward and personal moral conflict. The EEG and sLORETA help to confirm that not only cortical areas, but also the oscillation of brain frequencies participate in the regulation of decision-making behavior in depressed patients. It´s important to understand which pharmacological approach could improve the decision-making process in major depression.

Biography:

Effects of serotonin selective reuptake inhibitor – fluoxetin – on ethological parameters of anxiety state in lifted cross-like maze in emotionally stable (ES) and emotionally non-stable (ENS) to acoustic stressful stimulus (differed by seizure reaction) male Wistar rats, which are charac¬terized by different levels of biogenic amines in the brain structures, were studied. It was shown that ENS rats are originally differed by upregulation of serotonin (5-HT) and dopamine (DA), whereas ES rats – with upregulation of noradrenaline (NA). The results showed that all animals receiving fluoxetin demonstrated increased anxiety relatively to the controls. Anxiety behavior had different forms of manifestation. It is proposed that different characters of manifestation of anxiety in the rats with different phenotypes of nervous system are related to different character of effect of 5-HT upregulation on serotonergic receptors having different presentation and expression levels in the ES and ENS rats due to original significant differences in 5-HT levels in the nervous system of these animal groups. Biochemical analysis after fluoxetin administration revealed in the ENS animals predominant downregulation of 5-HT accompanied with upregu¬lation of NA in the hypothalamus. In contrast, in the ES rats significant down-regulation of 5-HT accompanied with significant upregulation of DA, while in the frontal cortex of these animals significant upregulation of 5-HT with reciprocal downregulation of DA, involved in anxiety state control and being prominent regulator of motor activity, was noticed. So, it is proposed that fluoxetin upregulates neurochemical indexes of anxiety state due to engagement of both systems of 5-HT and catecholamines which in this case act as reciprocal ones.

Abstract:

Effects of serotonin selective reuptake inhibitor – fluoxetin – on ethological parameters of anxiety state in lifted cross-like maze in emotionally stable (ES) and emotionally non-stable (ENS) to acoustic stressful stimulus (differed by seizure reaction) male Wistar rats, which are charac¬terized by different levels of biogenic amines in the brain structures, were studied. It was shown that ENS rats are originally differed by upregulation of serotonin (5-HT) and dopamine (DA), whereas ES rats – with upregulation of noradrenaline (NA). The results showed that all animals receiving fluoxetin demonstrated increased anxiety relatively to the controls. Anxiety behavior had different forms of manifestation. It is proposed that different characters of manifestation of anxiety in the rats with different phenotypes of nervous system are related to different character of effect of 5-HT upregulation on serotonergic receptors having different presentation and expression levels in the ES and ENS rats due to original significant differences in 5-HT levels in the nervous system of these animal groups. Biochemical analysis after fluoxetin administration revealed in the ENS animals predominant downregulation of 5-HT accompanied with upregu¬lation of NA in the hypothalamus. In contrast, in the ES rats significant down-regulation of 5-HT accompanied with significant upregulation of DA, while in the frontal cortex of these animals significant upregulation of 5-HT with reciprocal downregulation of DA, involved in anxiety state control and being prominent regulator of motor activity, was noticed. So, it is proposed that fluoxetin upregulates neurochemical indexes of anxiety state due to engagement of both systems of 5-HT and catecholamines which in this case act as reciprocal ones.

Biography:

Rafeeq Alam Khan is the Chairperson Department of Pharmacology, University of Karachi. He has published more than 100 papers in reputed journals and has been serving as an Editorial Board Member of repute.

Abstract:

Anxiety and depression are major disorders, caused by multiple factors including stress. Hence adjustment in life style can reduce the risk of these disorders. The growing awareness of relationship between food and health has revolutionized the food industry to maximize nutritional value of food products for improving health. Plants, fruits and vegetables have been a valuable source of natural products since long time, thus use of natural products has become increasingly popular among consumers to maintain health. Interestingly plant extracts, vegetables, fruits and their juices, rich in variety of nutrients and bioactive compounds, can be of great significance in therapeutics and have been screened for their potential uses as alternative remedies for many diseases. Present study describes a new behavioral model for testing antianxiety and antidepressant activity; hence this study was designed to evaluate juices of Citrus limon, Punica granatum and their combination on behavioral activity in rats. Rats were tested for their high motor activity, CNS stimulant effect and low anxiety like behavior using elevated plus maze and open field test, while antidepressant activity was determined by increased mobility of rats in forced to swimming test. C. limon and P. granatum juices were each administered in three different doses i.e. 0.2, 0.4 and 0.6ml/kg, and 2, 5 and 8 ml/kg respectively. C. limon at 0.4 ml/kg produced maximum CNS stimulant, anxiolytic and antidepressant effects in rats, while P. granatum produced significant CNS stimulant, anxiolytic and antidepressant activity at 5 and 8ml/kg. C. limon + P. granatum was also given in two combination doses i.e. 0.4 + 5ml/kg and 0.2 + 8ml/kg respectively. However combination of 0.4 + 5ml/kg produced significant anxiolytic, CNS stimulant and antidepressant effect, on the basis of these results it may be concluded that C. limon at 0.4 ml/kg, P. granatum in dose dependent manner and combination dose of C. limon and P. granatum at 0.4 + 5ml/kg may be used effectively as anxiolytic and antidepressant.

Biography:

Abstract:

The concept of risk currently used when considering the idea of deep space flights is represented by a generalized dosimetric functional as the criterion and quantitative measure of the danger of space types of radiation. The generalized dose comprises the doses inducing the immediate and long-term effects. The immediate radiation-induced effects develop during the flight, while the long-term ones, during later life. To calculate the dose for the immediate and long-term effects of radiation exposure, the coefficients are introduced that express the influence of the following factors on the radiobiological effect: the quality of radiation (including protons and heavy charged particles of different energy), time distribution of the dose, human body distribution of the dose, and modification of the organism's radiation response due to other flight factors. As the immediate radiation exposure effects, considered are the disorders of marrow hematopoiesis, cutaneous covering, and other organs and tissues of the organism. Regulations usually associate the long-term effects of cosmonauts' radiation exposure with the development of neoplastic processes in the organism, the risk of tumor development being considered the main adverse consequence for the interplanetary flights. At the same time, it should be noted that heavy charged particles of the galactic cosmic rays (GCR) have a highly destructive effect on the biological structures ‒ they have to be considered an extremely dangerous radiation factor that can cause crew's operator activity disorders already during the flight. This approach is supported by results of the experiments in which animals (rodents) were irradiated at charged particle accelerators at doses matching real fluxes of GCR heavy nuclei during a flight to Mars: in the post-irradiation period, disorders of spatial orientation and cognitive functions were observed. The authors link these neurobiological effects to a glutamatergic synaptic transfer disorder ‒ first of all, in hippocampus neurons. This is also indicated by the data showing a decrease in the level of a number of other neurotransmitters in different brain parts and behavioral reaction disorders in rodents after heavy ion irradiation. In experiments on 500 MeV/nucleon carbon ion irradiation of primates (Macaca mulatta) at a dose of 1 Gy, a reliable decrease of cognitive functions and the concentrations of metabolites (in particular, serotonin) was observed in animals of the excitable unbalanced type of higher nervous activity. To take into account the high biological effectiveness of high-energy heavy charged particles in radiation risk evaluation for manned interplanetary flights, the concept of "the successful completion of the mission" was introduced. Unlike the currently used radiation risk concept, which brings into the foreground the risk of cancer development ‒ the long-term effects of the exposure, the new paradigm is concerned, first of all, with the risk of disorders of higher integrative functions of the crew members' central nervous system. These disorders can impair cosmonauts' operator functions already during the flight and endanger the successful completion of the mission.

Biography:

Esposito Emanuela has completed first PhD in 2003 in Drug Science and second PhD in 2010 in Clinical Neurobiological Sciences at Universiy of Naples Federico II and University of Messina, respectively. Now, she is Associated Professor in Pharmacology at the University of Messina. She won many awards such as Umberto Veronesi Foundation Prize, Benedicenti Awards and Young Investigator Awards by Joint ASPET/BPS Society. She has published more than 180 papers in International journals. She attended 89 talks in many national and internationl meetings.

Abstract:

Mammalian target of rapamycin (mTOR) pathway signaling governs different cellular responses, including induction of autophagy and cell survival. Spinal cord injury (SCI) is a serious and debilitating health problem that usually causes lifelong disability and leads to neurological dysfunction. We hypothesized that mTOR pathway inhibition would diminish neuroinflammation and prevent neuronal death in a mouse model of SCI. SCI was induced in mice by the application of an aneurysm clip at T6-T7 level. mTOR pathway inhibition was achieved with rapamycin (a mTOR inhibitor), or temsirolimus (rapamycin analogues), or KU0063794 (a dual mTORC1and mTORC2 inhibitor) following spinal cord trauma (1 and 6 hours), and then for 3 subsequent days. Phospho-activation of the mTOR effectors p70S6kinase and ribosomal S6 protein and expression of infammatory parameters in perilesional area were assayed at 24 hrs, 48 and 72 hrs. Neuronal cell death was evaluated, autophagy was measured using Beclin-1 and LC3II expression. Iba-1 labeled, activated microglia were quantified. Neuronal death, and numerous Iba-1 labeled, activated microglia were evident at 24 and 48h following SCI. Rapamycin or KU0063794 treatment significantly reduced mTOR signaling, neuronal death, and microglial activation, coincident with enhanced expression of Beclin-1 and LC3II, markers of autophagy induction. KU0063794 was able to blunt the neuroinflammation better than rapamycin and temsirolimus. Persistent mTOR signaling following SCI suggests a failure of autophagy induction, which may contribute to neuronal death. These results suggest that mTOR signaling may be a novel therapeutic target to reduce neuronal cell death in SCI

Biography:

Cohen-Armon M has BSc in Chemistry and DSc in Physiology and Biophysics from the Technion, Israel. On 2001, she was a Visiting Researcher in Columbia University, New York, lab of Learning and Memory. She is a Faculty Member at the Tel-Aviv University Faculty of Medicine, Department of Physiology and Pharmacology and the Sagol School of Neuroscience.

Abstract:

Unexpectedly, a post-translational modification of DNA-binding proteins initiating the cell response to single-strand DNA damage is also required for long-term memory acquisition in a variety of learning paradigms. Our findings disclose a molecular mechanism based on PARP1-Erk2 synergism, which can underlie this phenomenon. This mechanism is activated by a high frequency electrical stimulation inducing Erk phosphorylation. PARP1 binding to phosphorylated Erk2 via docking sites in the catalytic domain of PARP1, caused PARP1 activation that mediated the recruitment of PARP1-bound phosphorylated Erk2 to promoters of Immediate Early Genes (IEG) implicated in synaptic plasticity and long-term potentiation (LTP). PARP1 inhibition, silencing, or genetic deletion abrogated both stimulation-induced IEG expression and LTP induction. They were similarly abrogated by a predominate binding of PARP1 to single-strand DNA breaks that occluded the binding sites of Erk in PARP1. These findings outline a PARP1-dependent mechanism governing Erk-induced IEG expression implicated in synaptic plasticity. It may underlie the pivotal role of polyADP-ribosylation in long-term memory acquisition, and the deterioration in learning abilities most frequently experienced in senescence.

Biography:

Galila Agam holds a PhD and is Full Professor of Biochemistry in Psychiatry since 2009 at the Ben-Gurion University of the Negev. She is the Past Chairperson of the Department of Clinical Biochemistry and Pharmacology and the Director of the Psychiatry Research Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel. She has published more than 150 papers in reputed journals, wrote 50 chapters in books/collective volumes, edited one book and three international journals' special issues and won numerous prestigeous research grants.

Abstract:

Compromised neuroplasticity and neuroprotection, mitochondrial and autophagy-dysfunction and neuroinflamation are implicated in the pathophysiology of bipolar-disorder, neurodevelopmental disorders and neurodegenerative disorders including ALS. Lithium, the prototype drug for bipolar-disorder, is neuroprotective. Among molecular effects the drug modulates the phosphatidylinositol system. It causes build-up of brain inositol-phosphates and depletion of free-inositol due to inhibition of the brain-abundant inositol-monophosphatase (IMPase)-1, and reduces mRNA levels of the sodium-myo-inositol transporter (SMIT1). IMPase-1 is encoded by IMPA1. Knockout of each of IMPA1 and SMIT1 in mice results in behavioral alterations found in lithium-treated mice. We carried out a DNA microarrays study, MS-MS proteomics accompanied by Westernblot analysis and multiplex cytokines protein levels analysis in the frontal-cortex of chronic lithium-treated mice [food supplementation, mean blood-levels 0.89 mEq/L±0.43 (S.D.)] and in IMPA1- and SMIT1-knockout mice. Pathway analysis of the microarrays results indicated transcriptional effects common to lithium-treatment and to each of the knockouts culminating in increased mitochondrial-function. The proteomic study indicated that enhanced autophagy is common to lithium-treatment and IMPA1-knockout. Both lithium-treatment and IMPA1-knockout reduced the levels of seven hippocampal pro-inflammatory cytokines by 56-73%. The results strongly suggest that unlike some of the previous ALS studies in rodents and humans an appropriate regime of chronic lithium-treatment, reaching blood-levels that are therapeutically-relevant in bipolar-disorder, induces augmentation of mitochondrial-function and autophagy and modulates neuroinflammation. Therefore, the potential beneficial effect of lithium for neurodegenerative disorders, in general, and ALS, in particular, deserves serious attention.

Biography:

Anil Kumar is a Professor of Pharmacology at Panjab University, Chandigarh. His research interest includes Neurodegenerative and neuropsychiatric problems including diabetic complication (neuropathy and nephropathy). He has published 166 Research Papers and 5 Book Chapters. He has received various awards and honors such as ICMR Award for Biomedical Scientist (2015), Rasthra Ratan Award (2014), Chandra Kanta Dandiya Prize (2014), APTI’s Pharmacy Teacher Award (2011), AICTE Career Award (2007), Young Investigator Awards- Rafaelsen Young Investigator award (2007), Lilly fellows award (2007), Fellowship Awards- INSA visiting fellowship (2005), BOYSCAST fellowship (2010), ICAD fellowship (2010), Riken Brain Science Fellowship, Japan (2007).

Abstract:

Traumatic Brain Injury (TBI) is turning out to be a major cause of disability and death. Recent research has revealed the possible role of neuroinflammation, oxidative, nitrosative stress and apoptosis in the pathophysiology of TBI as well as its related complications such as cognitive dysfunction and depression. Presently, symptomatic treatment is being given depending upon the patients and their clinical conditions. Different drug treatments (neuroprotectants) are used to treat and manage the traumatized patients. Therefore, the present study highlights the potential opportunity of different antioxidants/neuroprotectants and their neuroprotective mechanisms in the treatment of traumatic brain injury in experimental animals. The present study would also highlight the potential therapeutic effects of these plant based drugs. These studies further provide a hope that these drugs could be used effectively for the treatment and management of TBI and related complications.

Biography:

Doctor Bita Shalbafan is an Adult clinical Neurologist since 1998 and a consultant neurologist at t Labbafinejad Hospital. She has 12 years of experience in the field of multiple sclerosis and she is the member of MS Society Board and editor in chief of local MS magazine. She had undergone training activities including mitochondrial diseases and MS , Myology, Epilepsy and Neurogenetics. Since 2012 Following a visit to her collaboration with Professor Antonio Federico in Siena university ,Italy, then she began her researchs in the field of Late Onset Neurometabolic diseases such as Niemman Pick c, Fabry, Gaucher, Friedriech Ataxia, Leukodystrophies and Mitochondrial disorder

Abstract:

NPC is a metabolic disorder with a wide range of clinical presentation .There is not definite causes to this variety. In this case presentation, there are three patients in one family with same mutation, but different clinical presentations. We detected a previously unreported mutation in exome 16 of the NPC1 gene, c.2476_2484del (p.Ser826_Leu828del). This is an in-frame mutation that causes the loss of 3 amino acid residues. To date, this variant is not described in the Exome Aggregation Consortium, Exome Sequencing Project or the 1000 Genomes Browser and it is the first time we detect this variant based on Centogene’s mutation/variation database (CentoMD®). Based on this family genetic counselling and other relevant family members, to explain the results and address any concerns by testing a second independent sample from the patient in order to confirm the results (CMGS best practice guidelines) and testing the parents to confirm homozygosity by excluding the presence of a large deletion, also the concentration of the biomarker NPC - 509 is pathologically increased, therefore we considered this mutation as disease-causing. The first case is a 27 years old lady that complaints progressive unsteadiness since 10 years ago, the additional symptoms are dysphagia and dysphonia and impaired eye movement in vertical gaze that causes frequent fallings.In recent neurologic exam she had impaired cerebellar sign in both hands and feet with truncal ataxia normal proprioceptive sense and normal visual acuity. Normal motor exam and normal DTR in cranial nerve exam, slow vertical saccade and pursuit in eyes that confirmed by "eye see camera” test and bulbar signs in palatal movements are positive findings also she had near normal mental activity. Paraclinic findings include mild cerebellar atrophy in brain MRI and normal electomyography and nerve conductive study normal electroencephalography normal laboratory findings in liver and thyroid functions and electrolytes and peripheral blood cells and copper metabolism. The second case is a 25 years old man that is the brother of the first case .His disease presented in psychiatric feature after he was 18 and was graduated in high school, with a psychotic attack then he is on the antipsychotic drugs up to now, he is psychologically control except mild obsession in thought and mental activity is near to normal .In neurologic findings; no positive findings except impaired vertical eye movement in downward gaze. Only abnormal paraclinical finding is slow downward saccade in "eye see camera" test. The third case is a 45 years old that is the son of aunt (sister of their father) of the both previous cases. His disease presented in progressive supranuclear palsy since he was 35 Y/O. Frequent and progressive seizure type fallings was his chief complaint then. Neurologic exam shows impaired vertical eye movements in both eyes and mild cognitive impairment and mild dysphonia and dysphagia but there was severe cortical and brain stem atrophy in his brain MRI, no any other paraclinical findings. Nobody of these cases had no history of liver dysfunction in their lifetimes.

Biography:

My name is Mohamed hamdy Ibrahim, Egyptian, born on 1/11/1975. I have been graduated form, FACULTY OF MEDICINE, AIN SHAMS UNIVERSITY, CAIRO, EGYPT. I joined the neuropsychiatry residency at Ain shams university Cairo, Egypt from 2001 till 2003, finished my MD in neurology and got my doctorate by 2008. I have been assigned as Assistant professor of neurology and my main concern was in the field of NEUROVASCULAR INTERVENTIONAL RADIOLOGY. I finished my fellowship in interventional neurology at ZURICH University, Switzerland as F.I.N.R. by 2013. Now I am an Assistant clinical professor of neurology, GMU University and THUMBAY hospital, DUBAI, Ajman, united Arab of emirates (UAE) SINCE 2010. I had some publications in many journals as OPEN JOURNAL OF MEDICAL IMAGING (OJMI), The Egyptian Journal of Radiology and Nuclear Medicine, the European Journal of Neurology, In addition I am Member of World Federation of Interventional and therapeutic Neuroradiology (WFITN), Member of ESMINT (European Society of Minimal Invasive Neurological Therapy). Member of European Society of Neuroradiology Diagnostic and Interventional (ESNR)

Abstract:

Focal Dystonia in young aged patients considered to be uncommon clinical presentation, unless a secondary cause to be considered. Infarcts of the corpus callosum are rare and have not been well documented previously. As for a variety of signs and symptoms due to corpus callosum lesion. Focal dystonia can be easily overlooked.

Biography:

Dr. Fauzan Alam Hashmi is a resident in Section of Neurosurgery at Aga Khan University Karachi, Pakistan. He completed his MBBS in 2010 and internship in 2011, and has been associated with Department of Surgery since January 2013. He has presented his studies in Annual Meetings in American Association of Neurosurgery and European Association of Neurosurgical Societies in 2014. He has 4 published articles in reputed journals.

Abstract:

Objective: Clear cell variant in ependymal tumors is rare. We aim to compare the features, clinical outcomes of clear cell variant with the classic pathology of grade 3 intracranial ependymal tumors in Pakistan. Materials & Methods: A retrospective cohort study conducted at the department of Neurosurgery, Aga Khan University. The medical record files from 2003 – 2014 were reviewed. MRI/C.T scans and histopathological slides of WHO Grade III ependymal tumors were reviewed. Analysis was done on SPSS 20. Results: There were 9 cases of clear cell variant and 23 cases of classic anaplastic ependymoma. The median age of clear cell variant cases was 52 years (range 24years-72 years), whereas that of anaplastic ependymoma cases was 37 years (range 3 months to 65 years). Symptoms included Headache 66% in CCE and 63% in AE, seizures 30% in CCE and 22% in AE, and raised ICP in 30% in CCE and 54% in AE. CCE was supratentorial in 70% cases, intracranial anaplastic ependymoma was supratentorial in 58% of cases. Gross total resection was achieved in 55% cases in CCE and 26% cases in AE. Subtotal resection was done in 45% cases in CCE and 65% in AE. Radiotherapy was given in 55% patients in CCE and in 52% in AE. Recurrence was there in 77% cases of CCE and 70% in AE. Repeat surgery was done in 30% cases of CCE and 34% cases of AE. Median progression free survival was 9 months (range 3-28 months) and overall survival was 13 months (range 3-41 months) in CCE. Median progression free survival was 14 months (range 0.5-53 months), and overall survival was 18 months (range 1.5- 36 months) in AE. Survival Analysis using Log Rank values showed age< 55 and radiotherapy to be significant prognostic factors. Survival analysis of the two histopathologies showed Clear cell Ependymoma to be 1.86 times worse in prognosis than Anaplastic Ependymoma. Conclusion: Clear cells in Grade III ependymal tumors are found mainly in adult population. Supratentorials show worse progression-free and overall survival than anaplastic ependymoma. Overall survival is significantly worse in our part of the world for Grade 3 ependymal tumors.

Biography:

Shashank Arunachal U pursued his medicine (MBBS) degree from K.S. Hegde Medical Academy from Rajiv Gandhi University. He is interested in psychopharmacology and has volunteered in ‘Community Intervention Programme in Schizophrenia Patients’ for period of 3 years a project run by National Institute of Mental Health & Neurosciences (NIMHANS) in a Taluk Headquaters (Local Governing Body). During this time he indulged himself in interviewing patients, psycho education of patients/family members, administering rating scales, blood sample collection, conducting home visits, co-ordinating follow-ups and entering the data. During this period he worked on 2 papers ‘Arecanut use in rural South Indian Schizophrenia Patients- a comparative study’ & ‘Epidemiology of Tardive Dyskinesias in Community dwelling Schizophrenia Patients in rural South India’. Currently, he is pursuing his 2nd year Post-graduation in Pharmacology at St. John’s Medical College. At present he is also working on ‘Drug- Induced Acute Akathisia: A Case-Control Study in Patients taking Neuroleptic Agents at a Tertiary Care Hospital’ as a part of his Post-graduation thesis project.

Abstract:

Tardive dyskinesia (TD) is a irreversible long-term adverse effect of antipsychotics. We report on prevalence and correlates of TD in sample of community dwelling schizophrenia patients. In our community intervention program from seven years, 350 schizophrenia patients have been identified. We conducted a cross-sectional study. Mini International Neuropsychiatric Interview is used for diagnosing schizophrenia according to ICD-10 criteria; Positive and Negative Syndrome Scale (PANSS) is used to assess psychopathology; Tardive Dyskinesia Rating Scale (TDRS) is used to assess tardive dyskinesias. Probable TD was defined according to Schooler-Kane research criteria. Severe TD was defined as either ‘continuous’ presence of movements or ‘incapacitating’ movements according to the TDRS. Mean (SD) age of the sample (n=180) was 43.5(11.5) years at baseline; females formed 49.4% (n=89); 89(50%) were from lower socio-economic strata; 96(53.6%) were married. Average years of education was 6.3(4.7) years; mean age at onset of schizophrenia was 28.4(9.9) years; Mean duration of illness was 180.9 (117.6) months. Mean total PANSS was 69.6 (25.1) at baseline; total duration of antipsychotic exposure was 53.4(26.4) months. Most of the patients were exposed to both typical as well as atypical antipsychotic medications. Prevalence of TD was 67/180 (37%). Severe TD was found only in 5 patients. Patients with TD were: significantly elder [age 46.3(12.8) vs. 41.8(10.4) years respectively; p=0.01] and had more severe current symptoms [mean current total PANSS score of 52.3 (20.0) vs. 44.6(15.1) respectively; p<0.01]. Prevalence of TD in our community sample is fairly high & presence of severe TD was very low.

Biography:

Joel Salinas is a research and clinical fellow in Behavioral Neurology and Neuropsychiatry at Massachusetts General Hospital. His research focuses on investigating psychosocial predictors and modifiable risk factors of age-related neurologic disease and its sequelae using large epidemiologic cohorts. His long-term goal is to develop and deploy interdisciplinary strategies to prevent the development of devastating chronic brain disease. After graduating from Cornell University, he completed medical school at the University of Miami Miller School of Medicine followed by neurology residency at the Massachusetts General Hospital and the Brigham and Women’s Hospital.

Abstract:

We describe a case of psychogenic non-epileptic seizures (PNES) as an example of what has been called the “demanding encounter” in clinical neurology. Patients in these encounters are more likely to see themselves as informed consumers who expect to receive requested diagnostic tests and treatments from healthcare providers, potentially creating a conflict over treatment goals and appropriate limit setting. “Demanding encounters” are associated with physician burnout and patient dissatisfaction. We survey some of the ethical frameworks introduced to navigate this type of encounter. We argue that physicians are obligated to identify the underlying beliefs that are leading to requests for unnecessary testing and treatment and that, by addressing these beliefs, providers have the best chance of establishing a respectful, meaningful therapeutic relationship with their patients.

Biography:

Farhan Ahmad is a joint B.S./M.D. candidate at The University of Texas at San Antonio with interests in public health, neurosurgery, and neuroethics. He is the co-founder of VideoMed, a project dedicated to providing free mental healthcare to the homeless, which has been featured on Xconomy, Fox, and NPR affiliates. Farhan has also presented his work on Alzheimer’s disease at the United Nations General Assembly and collaborated with non-governmental organizations to develop student-led global health projects in Peru. He has been a visiting scholar at The Hastings Center and summer fellow at Yale University.

Abstract:

Although Big Data has the potential to accelerate scientific research output, ethical frameworks for its use and implementation in Alzheimer’s Disease (AD) research is forthcoming and much-needed. For years, research on AD has been focused on a variety of biochemical interactions that may contribute to the clinical phenotype, from amyloid B plaques and Tau neurofibrillary tangles to the APOE4 gene. Despite years of research on the pathogenesis of AD, 99.6% of clinical trials from over the past decade have failed to deliver a reliable cure. [1] Although the reason for this failure cannot be directly attributed, the authors propose that the misuse of Big Data may in fact worsen this problem, as statistical errors and epistemological fallacies of approach could be exacerbated with larger volumes of more attractive data. Therefore, there is a need for an ethical framework that contextualizes the realistic use of Big Data in AD research, based on current attitudes in the political milieu and limits in computing power. The authors analyze the impacts of Big Data on AD research thus far, as well as describe the policy landscape to postulate a modular framework that takes into account neuroethical concerns of patient privacy and research economics, stemming from the advent and use of Big Data. Since our current understanding of AD has not generated fully successful therapeutics, there are conceptual gaps that must still be bridged, and ethical applications of Big Data could be at the mainstay of that inquiry.

Biography:

Angela Gauthier is a third year medical student at the Yale School of Medicine. She majored in Neuroscience at Dartmouth College and graduated with High Honors. She has written several journal articles and is a contributing author to First Aid for the USMLE Step 1, 2016 edition (McGraw Hill, 2016).

Abstract:

Clobazam is an oral 1, 5-benzodiazepine used worldwide for the treatment of many types of epilepsies, although it is currently only approved for Lennox–Gastaut syndrome in the USA. This anticonvulsant and anxiolytic therapeutic has repeatedly demonstrated great efficacy and a high safety profile in refractory epilepsy as well as in a few monotherapy trials in both children and adults. Clobazam allosterically activates the GABAA receptor, and it binds less to subunits that mediate sedative effects than other benzodiazepines. It acts quickly, maintaining a therapeutic effect for a long duration due to its active metabolite, N-desmethylclobazam. Dosage is between 5 mg and 40 mg a day, depending on patient weight, efficacy, and tolerability. Efficacy tolerance has not been a problem in the best studies. Clobazam has provided many benefits to epileptic patients. It should be used by clinicians early as an adjuvant therapy in the treatment of refractory epilepsy and even considered as monotherapy in a broad spectrum of epilepsy syndromes.

Biography:

Mark Miller is a PhD student at the University of Edinburgh, working with Andy Clark. His research focuses on the interelationship between the feeling body and the Bayesian brian.

Abstract:

In this programmatic paper we explain why a radical embodied cognitive neuroscience is needed. We argue for such a claim based on problems that have arisen in cognitive neuroscience for the project of localizing function to specific brain structures. The problems come from research concerned with functional and structural connectivity that strongly suggests that the function a brain region serves is dynamic, and changes over time. We argue that in order to determine the function of a specific brain area, neuroscientists need to zoom out and look at the larger organism environment system. We therefore argue that instead of looking to cognitive psychology for an analysis of psychological functions, cognitive neuroscience should look to an ecological dynamical psychology. A second aim of our paper is to develop an account of embodied cognition based on the inseparability of cognitive and emotional processing in the brain. We argue that emotions are best understood in terms of action readiness (Frijda 1986, 2007) in the context of the organism's ongoing skillful engagement with the environment (Rietveld 2008; Bruineberg & Rietveld 2014; Kiverstein & Rietveld 2015). States of action readiness involve the whole living body of the organism, and are elicited by possibilities for action in the environment that matter to the organism. Since emotion and cognition are inseparable processes in the brain it follows that what is true of emotion is also true of cognition. Cognitive processes are likewise processes taking place in the whole living body of an organism as it engages with relevant possibilities for action.

Biography:

Yash Patel has completed his bachelors degree in Health Sciences at McMaster University and is currently pursuing his medical doctorate at University of Toronto Medical school. Yash has extensive research experience in neurodegenration in Huntington’s disease working under the supervision of Dr.Ray Truant – the Chair of the Scientific Advisory board of Huntington’s society of Canada. Yash also has conducted research on the brain-gut axis at the Brain-Body Institute at St.Joesph’s Hospital in Hamilton, Ontario

Abstract:

Huntington’s disease (HD) is characterized by a variety of aberrations in basic cellular processes, including epigenetic dysregulation –attributed to the downstream effects of mutant huntingtin. The phosphorylation of two serine residues within the first 17 amino acids (N17) in huntingtin is critical in modulating the toxicity of mutant huntingtin. Increase in N17 phosphorylation has been shown to ameliorate HD pathology, presenting a novel pharmaceutical target. Epigenetic compound inhibitors were screened for N17 phosphorylation, and restoration of normal epigenetic regulation within two cellular models of HD; ST Hdh Q111/Q111 (inactive p53) and TruHD hTERT fibroblasts (active p53). There is a drastic effect by histone deacetylase inhibitors (HDAC) on the level of N17 phosphorylation. Furthermore, the p53-active TruHD hTERT cell line is affected by a variety of different epigenetic compound classes such as, PARP, Aurora kinase inhibitors etc., in addition to the HDAC inhibitors found only to be effective in the p53-inactive ST Hdh Q111/Q111 cell line. The difference in compound hits between the hTERTs and ST Hdh demonstrates the importance of having active p53 to model the true cellular physiology in Huntington’s disease. Most importantly, high content screening for molecular therapeutics should screen through TruHD hTERTs, rather than the commonly used striatals ST Hdh Q111/Q111s.

Biography:

Filip Tyls (1985, Prague, Czech Republic) is a psychiatrist and neuroscientist with main interest in translational mopdels of acute psychosis and psychedelic substances. He completed 1st medical faculty and currently is PhD student in neurosciences on 3rd medical faculty on Charles University in Prague. He recieved a specialization in electroencephalography and is in training of Gestalt psychotherapy. He has experiences as psychedelic sitter in a team working on pilot clinical trial with psilocybin in Czech republic. He has published several papers in local as well as foregin journals (e.g. review Psilocybin – summary of knowledge).

Abstract:

The serotonergic hallucinogen psilocybin, has profound effects on the human mind, which can be characterized by alteration in perception, thinking disorder and strong emotional salience. The character of the altered state of consciousness induced by hallucinogens is hardly predictable; while an important role has the environment in which psilocybin is administered (setting). Recent works showed that psilocybin-induced altered state of consciousness has a potential in the treatment of some psychiatric disorders. Twenty volunteers completed the psilocybin (0.26mg/kg) session in a double-blind, placebo-controlled arrangement in a living-room-like setting. This study describes the phenomenology, physiological parameters, pharmacokinetics of psilocybin intoxication and focuses on electrophysiological measures of brain activity. The effects of psilocybin peaked in 60 minutes and subsided after 6 hours. Psilocybin induced mydriasis, an increase in blood pressure and heart rate. A significant increase of psychopathology was documented by Brief Psychiatric Rating Scale and Altered States of Consciousness Scale. Psilocybin decreased the EEG spectral power in alpha frequency band, however increased the power of gamma oscillations. The LORETA analysis revealed the source of decreased alpha in midline parietal structures and occipital lobes. The increase in higher frequencies was pronounced in large temporal areas. EEG findings will be correlated with neuropsychiatric scales. We confirmed the safety and beneficial effects of psilocybin administration under controlled experimental conditions. The decrement of EEG alpha activity was observed mainly in brain structures involved in Default Mode Network, which is thought to represent introspective processes. These findings will help facilitate future clinical trials using psychedelics in patients.

Biography:

Gerson has started his PhD at the age of 21 years in the Federal University of Rio de Janeiro and published its first paper as a first author at the age of 22. Since then, he began working with animal models of schizophrenia and also directly with schizophrenia patients. His current research focus on developing cognitive training strategies to treat cognitive deficits in schizophrenia while also investigating the effects of training in the brains of rodents using a variety of molecular, pharmacological and imaging studies.

Abstract:

D-serine is an endogenous co-agonist of NMDA receptor, which plays a crucial role in many aspects of cognition. Animal research suggested that the co-agonist site was not saturated, and subsequent studies demonstrated that d-serine administration improved rodent’s performance in many memory tasks. Recently, D-serine pro-cognitive effects were observed even in healthy adults and in the elderly. In addition, given the important role of D-serine in cognition, there was growing interest to find out whether its pathway was affected in psychiatric disorders. So far, D-serine has mostly been implicated in the etiology of schizophrenia. For instance, animal models with decreased D-serine levels recapitulated many endophenotypes of the disorder. Lower D-serine levels have been found in cerebrospinal fluid and in the blood of patients with schizophrenia, and evidence indicates a higher activity of the enzyme responsible for metabolizing D-serine, D-amino acid oxidase, in post-mortem brains of the patients. In intervention studies, D-serine added to antipsychotics had a moderate effect in treating the cognitive deficits and negative symptoms. In sum, D-serine has a great potential as a cognitive enhancer in healthy adults and in patients with schizophrenia. However, I’ll address many questions that need to be solved, regarding D-serine pharmacokinetics, possible side-effects, other strategies to increase its levels and combination with other therapies to increase efficacy.

Biography:

Abstract:

Brain vulnerability to inflammation is high during the early postnatal age and perinatal infection could result in long-lasting neuropsychiatric disorders including autism and schizophrenia, and mood disorders including depression. In the present study we have assessed the efficacy of an extract of the medicinal plant Thymelaea lythroides to counteract hippocampal microglia activation and depressive-like behaviors in adulthood in male rats that were injected with LPS at 14 days of age. The effect of Thymelaea lythroides extract was compared to the effect of minocycline, a molecule known to inhibit microglia activation. Our findings indicate that LPS injected animals showed in adulthood high levels of TNF  and Iba1 immunoreactivity in the hippocampus and significant depressive-like behavior in forced swimming test and anxiety-like behavior in elevated plus maze test. Thymelaea lythroides extract and minocycline had similar actions in counteracting the effects of perinatal LPS.