Day 3 :
- Track 5: Neurochemical Transmission
Track 7: Chemical Neurotransmitters
Track 8: Neurotechnology
Track 12: Neuroethics
Track 13: Future Aspects of Neuropharmacology
Location: Hilton San Antonio Airport
Session Introduction
Jose F Abisambra
University of Kentucky, USA
Title: PERK inhibition reduces hyperphosphorylated tau and rescues neuronal function in an eIF2 Α-independent mechanism
Time : 09:00-09:20
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 eIF2ï¡. 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.
Cristina Vittoria Dieni
University of Perugia, Italy
Title: Low excitatory innervation of immature neurons enhances pattern separation
Time : 09:20-09:40
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.
José R Sotelo
Instituto de Investigaciones Biológicas Clemente Estable, USA
Title: Glia to axon RNA transfer
Time : 09:40-10:00
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.
Xavier F. Figueroa
Pontificia Universidad Catolica de Chile, Chile
Title: Central role of nitric oxide-dependent S-nitrosylation in the control of the astrocytic Ca2+ signaling that mediates neurovascular coupling
Time : 10:00-10:20
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.
Anna PuigdellÃvol-Sánchez
University of Barcelona, Spain
Title: Future individualization of intrathecal dosages and paramedian approaches to reduce toxicity and bone contact: Estimating Cerebrospinal fluid dilution volumes and puncture angles from MRI
Time : 10:20-10:40
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.
Stephanie C Joachim
University Eye Hospital, Ruhr-University Bochum, Germany
Title: Inflammatory demyelination induces retinal ganglion cell loss and glia response in experimental autoimmune encephalomyelitis
Time : 10:40-11:00
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.
Enzo Wanke
University of Milano-Bicocca, Italy
Title: Investigation of the neuropharmacology of fast and slow drug-induced interactions in networks of astrocyte-neuron-microglia using advanced in vitro multi-site recording methods
Time : 11:15-11:35
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.
Abid Oueslati
Université Laval School of Medicine & CHU de Quebec Research Center Quebec, Canada
Title: α-synuclein phosphorylation as a therapeutic target in Parkinson's disease and related disorders
Time : 12:30-12:50
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 Sïƒ E/D or Sïƒ 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.
Ahmed K Salama
Majmaah University, Saudi Arabia
Title: Oxidative damage and pharmacokinetics of the benzonitrile herbicide, pendimethalin in rat
Time : 13:30-13:50
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.
Marina Zueva
Moscow Helmholtz Research Institute of Eye Diseases, Russian Federation
Title: The theory of fractality of sensations and the brain health
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."
Miguel A Morales
Universidad Nacional Autónoma de México
Title: Neurotrophins modulate synaptic plasticity of sympathetic ganglia
Time : 13:50-14:10
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.
- Young Researchers Forum
Location: Hilton San Antonio Airport
Session Introduction
Shashank Arunachal U
St. Johns Medical College, India
Title: Epidemiology of tardive dyskinesias in community dwelling schizophrenia patients in rural South India
Time : 14:45-15:00
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.
Joel Salinas
Harvard Medical School, USA
Title: Autonomy and the “Demanding Encounter†in clinical neurology
Time : 15:00-15:15
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.
Farhan Ahmad
The University of Texas at San Antonio, USA
Title: Constructing a Neuroethical Framework for Alzheimer’s Disease Research Employing Big Data
Time : 15:15-15:30
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.
Angela Gauthier
Yale School of Medicine, USA
Title: Clobazam: A safe, efficacious, and newly rediscovered therapeutic for epilepsy
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.
Mark Miller
University of Edinburgh, Scotland
Title: The embodied brain: Towards a radical embodied cognitive neuroscience
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.
Filip Tyls
National Institute of Mental Health Czech Republic
Title: Psilocybin Clinical Trial: Acute Effects and its relationship to the brain activity as measured by quantitative EEG
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.
Gerson Duarte Guercio
Federal University of Rio de Janeiro, Brazil
Title: D-serine as a cognitive enhancer in health and disease
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 ï¡ 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.