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

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: