9^th Global Neuroscience Conference November 21-22, 2016 Melbourne, Australia

Biography:

Ana Maria Enciu is assistant professor in Cell Biology at Carol Davila University of Medicine and  research assistant at Victor Babes Institute of Pathology. She has completed her PhD in neurosciences with a study on blood-brain barrier tight junction proteins.  She continued with a postdoctoral training in neurooncology. She has published more than 20 papers  and has been serving as an editorial board member for Austin Alzheimer’s and Parkinson’s Disease Journal since 2014. 

Abstract:

Background: Amyloid precursor protein (APP) is a membrane protein highly expressed in the brain, involved in the pathogeny of Alzheimer`s disease. Recently, protein dimers were reported to occur in vitro, with impact on pathologic metabolization and senile plaque formation.

Aim: Our study investigated whether the expression of APP is dependent on a membrane scaffolding protein – caveolin and if in native state APP can be found in dimeric or oligomeric complexes.

Material and method: brain cortex was prelevated from 7-9 mo old normal and caveolin knockout mice and investigated for amyloid precursor protein by reducing and non-reducing electrophoresis, followed by western blotting. Membranes were next separated by ultracentrifugation and investigated for APP containing macromolecular complexes by non-denaturating, blue native electrophoresis

Results APP expression was modified by the absence of caveolin, depending on the brain region. Electrophoretic separation of macromolecular complexes from mouse brain cortex was dependant on the extraction buffer and type of gel. No dimeric or low-rank oligomers were highlited with the selected protocols.

Conclusion: APP dimers were not present in the investigated brain regions even under mild protein extraction conditions. We propose that dimerization is either an in vitro occurrence, or is masked by association with another membrane proteins in macromolecular complexes.

Acknowledgment: This work was supported by a grant of the Romanian National Authority for Scientific Research and Innovation CNCS-UEFISCDI, project number PN-II-RU-TE-2014-4-1534.

Biography:

Weidong Le, M.D., Ph.D., is a neurologist/scientist with a major research interest in neurodegenerative disorders including Parkinson’s disease, Alzheimer’s disease and ALS. He graduated from Shanghai 2^nd Medical University with a doctoral degree in 1988, and received postdoctoral training at Dr. Stanley Appel’s laboratory from 1989-1991. He was promoted to Professor of Neurology in 2005 at Baylor College of Medicine, and since 2013 he has been appointed as the Director of Center for Translational Research on Neurological Diseases, and Vice President of 1^st Affiliated Hospital, Dalian Medical University. He is a full affiliate member of Houston Methodist Research Institute. He has published over 200 SCI papers in peer review journals and 7 scientific books, and serves as board member or associate editor for 8 international journals.

Abstract:

Amyotrophic lateral sclerosis (ALS) is an adult-onset devastating neurodegenerative disease resulted from the selective death of motor neurons (MNs) associated with abnormal protein aggregation in the spinal cord and brain. We have demonstrated that autophagy impairment may underlie the pathogenesis of ALS. Mutations in the genes encoding SOD1, TDP-43, OPTN and VCP can cause misfolding proteins and autophagy induction. It is still under debate whether autophagy has a protective or detrimental role in ALS. We have found that the macroautophagy is specifically activated in the MNs of SOD-1 mouse model of ALS at early stages. In addition, we have demonstrated that mTOR-dependent autophagy enhancer rapamycin treatment in the ALS animal model causes accumulation of AVs, but fails to reduce the level of mutant SOD1 aggregates, suggesting the abnormal autophagic flux in ALS. In addition, rapamycin treatment results in severe mitochondrial impairment, higher Bax levels and greater caspase-3 activation. On the contrast, application of mTOR independent autophagic enhancer trehalose prolongs the motor neuron survival and ameliorates autophagic flux defect in the ALS model. Recently a study of whole exome sequencing in 2,874 ALS patients vs 6,405 controls, identified TANK-Binding Kinase 1 (TBK1) as an ALS gene. TBK1 is known to bind to and phosphorylate a number of proteins involved in innate immunity and autophagy, including optineurin (OPTN) and p62 (SQSTM1/sequestosome). These observations reveal a key role of the autophagic pathway in ALS, which may provide useful information designing to target on autophagy for the potential therapeutic intervention of this devastating disease.

Biography:

Dr. Malykhina is Associate Professor at the University of Colorado Denver.  She directs a Neurourology laboratory focused on neurophysiology of the lower urinary tract and functional chronic pelvic pain disorders, with particular emphasis on the mechanisms underlying the processing of sensory nociceptive information, neurogenic bladder dysfunction in neurodegenerative disorders, and mechanosensitivity of the overactive bladder. Dr. Malykhina is a Center Director for the Colorado P20 Center on Interdisciplinary Research in Benign Urology supported by the NIH grant (P20-DK097819). She is an active member of many international societies, and serves on the review panels for the NIH and DoD study sections.

Abstract:

Multiple sclerosis (MS) is an auto-inflammatory disease of the CNS that affects approximately 400,000 people in the United States alone and more than 2.1 million people worldwide. Lower urinary tract symptoms (LUTS) are present in 70–80% of MS patients, causing great discomfort and having a negative effect on the quality of the individual’s social, occupational and sexual life. Neurogenic LUTS include urinary urgency, urinary incontinence, nocturia, urinary hesitancy, overflow incontinence, a sensation of incomplete emptying, urinary retention, and a weak urinary stream. The most common symptom reported by MS patients in remission is urgency of micturition followed by urinary frequency. In approximately 10–15% of patients, bladder symptoms are present at the onset of MS when there may be few lesions identified in the spinal cord and/or brain. In patients with established MS, bladder symptoms are prevalent and often associated with symptoms of bowel and sexual dysfunction. Identification and development of urinary tract protective therapies in neurological diseases has proven to be a major challenge, because of an already substantial LUT compromise at the time of presentation to a urologist. Therapeutic approaches for neurogenic LUTS primarily include anti-muscarinic drugs as well as intermittent self-catheterization to facilitate complete bladder emptying. Given the unfavorable side effect profile of these medications and poor persistence on therapy, as well as the burden of catheterization on a debilitated population, more innovative therapeutics are desperately needed.  In the quest for therapeutics, a greater understanding of the pathophysiology and patterns of disease is also required.  

Biography:

Abstract:

CONCLUSIONS AND RELEVANCE Criminal behavior is more common in patients with bvFTD and semantic variant of primary progressive aphasia than in those with AD and is more likely to be an early manifestation of the disorder. Judicial evaluations of criminality in the demented individual might require different criteria than the classic “insanity defense” used in the American legal system; these individuals should be treated differently by the law. The appearance of new-onset criminal behavior in an adult should elicit a search for frontal and anterior temporal brain disease and for dementing disorders.

Biography:

Edoardo Sinibaldi (MSc Aerospace Engineering, 2002, University of Pisa; Ph.D. Mathematics for Technology and Industry, 2006, Scuola Normale Superiore, Pisa; Post-Doc at The Biorobotics Institute, Scuola Superiore Sant’Anna, Pontedera), is with the Italian Institute of Technology since 2009, formerly as Senior Post-Doc, then as Researcher. His current research interests include biorobotics, in particular medical robotics, and modeling for biomedical applications. He serves as reviewer for nearly twenty journals. He has published one book, three book chapters, more than forty peer-reviewed papers, and two patents (by also demonstrating the first flexible probe able to physically build its track while being deployed).

Abstract:

Central Nervous System pathologies are one of the world's leading causes of disability. Despite the availability of advanced interventional techniques, many surgical tasks are still very challenging because of complex anatomical constraints. Moreover, in many cases therapy control in hampered by the lack of a thorough, quantitative understating of the related underlying physical phenomena. Both aspects motivate the development of novel approaches, including the introduction of robotic platforms and tools, and modeling frameworks.

On the robotics side, we will illustrate a platform that encompasses, in particular, a lightweight robot fostering synergistic robot–surgeon integration. We demonstrated its potential for mitigating some risk factors in neurosurgery by addressing a model ventriculostomy, in collaboration with neurosurgeons. At the tool level, we will illustrate a novel design approach that permits to achieve flexible scopes to be deployed over a given trajectory (the whole shaft, not only the tip), thus avoiding undesired/harmful contacts.

On the modeling side, we will address the numerical investigation of intrathecal drug delivery (ITDD) in the cervical subarachnoid space. The growing interest in ITDD is mainly motivated by its potential for bypassing the shielding effect of the blood-brain barrier to macromolecules. However, ITDD is affected by several parameters, many of which are little understood. We will show some recent results (obtained in collaboration with the University of Oslo and the University of Idaho) regarding the effects of catheter placement on ITDD, also encompassing drug transport to the cord.

Biography:

Abstract:

Introduction: anxiety is an emotional and physiological response to the internal felling of overall danger that is easily resolved. The aim of this study has been to determine the relationship between exam anxiety and the feeling of homesickness among non-native students.

Methodology: the present study is cross-sectional and the subjects in this study are 80 non-native male and female PhD candidates in clinical and physiopathology majors in 2013 academic year that have been evaluated with the help of Persian homesickness questionnaire and Sarason’s test anxiety questionnaire and the data was analyzed using Pearson’s correlation coefficient.

Results: With regard to the Pearson’s correlation coefficient there is a significant and reverse relationship between the desire to return to home and exam anxiety (r=0.0344, p=0.004) and there is a significant and reverse relationship between the Compatibility and exam anxiety (r=0.428, p<0.0001) and there is a significant and direct relationship between the feeling of alone and exam anxiety (r=0.888, p<0.0001).

Discussion and conclusion: there is a significant relationship between the feeling of homesickness and exam anxiety and the mental health of non-native students will be deteriorated by the feeling of homesickness and anxiety.

Biography:

Saman Azizi has completed his  M.D degree at the age of 26 years from Shiraz University of Medical science. He has published his paper in Global Journal of Health Science in the field of psychiatry with head of psychiatry department and He is working on 2 papers now.

Abstract:

Biography:

Dr Tayebi is a Senior academic at the University of Melbourne and heads the protein misfolding disease group. Dr Tayebi has previously very successfully led to satrt up biotechnology companies in the UK and the US.

Abstract:

An active and promising area of research for Alzheimer’s disease (AD) is immunotherapy using antigens (active) or antibodies (passive) that target AD neuropathology. Senile plaques contain the beta-amyloid (Aβ) peptide that is derived from a longer precursor protein, amyloid  precursor protein. Amyloid beta is produced as either a 40 or 42 amino acid peptide, the latter being more fibrillogenic and toxic than the shorter isoform. Initially produced as a soluble peptide, Aβ subsequently can form oligomers, a molecular complex of monomer units. Aβ oligomers are highly toxic to neurons and particularly damaging to synapses. There is strong evidence that oligomer accumulation may seed plaque aggregation and serves as an early molecular target for preventing AD. Interestingly, oligomers can be detected by antibodies based upon structure with less of a need to target the amino acid sequence of an individual protein making antibody development for oligomers a fascinating area to pursue. Antibodies developed against oligomers may be able to bind several misfolded proteins implicated in neurodegenerative diseases.

Immunotherapy studies have typically used transgenic mouse models of AD, and subsequently translated to human clinical trials. However, the success rate of these translational studies has been limited. In contrast, studies in another animal model, the aged canine, indicated that immunotherapy led to similar outcomes in AD clinical trials; reduced Aβ plaque pathology with no improvements in cognition but indications of a slowing of cognitive decline.

We have previously developped and chatacterized unique anti-Aβ single domain antibodies derived from camelids. These antibidies, we called PRIOAD, were able to (i) cross the in vitro and in vivo blood brain brain (BBB) in mice rats and in vitro human BBB model; (ii) bind with high affinity to soluble oligomers derived from synthetic and native human Aβ but not their monomeric and fibrils counterparts; and (iii) not induce neurotoxic effects and host mmune responses in mice.

PRIOADs were evaluated for their therapeutic efficacy in a pilot sutdy using aged beagles with  mild cognitive imparement. Following intraventricular infusion of PRIOAD for 3 months, there was a significant reduction of Aβ plaque burden in these animals. More importanly, PRIOADs led to reversal of the cognitive deficits in beagles.

The study was very encouraging and will be expanded to include larger number of animal cohorts prior to translation into human clinical trials.

Biography:

Majid Gharghani is one of the postgraduate pioneer students in field of neuroimmunology and neural stem cell culture. He has worked as a research and teaching assistant at the age of 25 years in Yasuj university of medical sciences, Iran. He also has attended several workshops to enhance his practical understanding of various in vivo and in vitro techniques including immunohistochemistry, immunofluorescence, neural stem cell culture and EAE models.

Abstract:

Multiple sclerosis (MS) is associated with a neuropsychiatric problems of which depression is the commonest. Also, antidepressant drugs are known to impact on the immune system and CNS cells. Aim of present study was to introduce an antidepressant drug with ameliorative effects on experimental autoimmune encephalomyelitis (EAE) severity, an animal model of MS, including spinal cord inflammation and demyelination.

In this study, the protective effect of fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), was investigated in cultured cultured embryonic neural stem cells (ENSCs) and rat model of acute EAE. First, we examined the effect of fluvoxamine on proliferation and differentiation of cultured ENSCs. Next, it’s immunomodulatory and oligodendrogenesis properties was investigated in EAE model of Lewis rats.

Results showed that fluvoxamine increases the viability and proliferation of ENSCs. Moreover, treatment of NSCs by fluvoxamine resulted in a significant increase in diferentation toward oligodendrocyte cells (MBP possitive cells) and also astrocyte cells (GFAP positive cells). IN vivo results of EAE rats, demonstrated that clinical outcomes of EAE were ameliorated in fluvoxamine- versus PBS-treated EAE rats. Fluvoxamine caused a significant decrease in serum IFN-γ, in comparison to PBS-treated EAE rats, while significantly increased serum IL-4 level. Furthermore, histopathological observations showed statistically decreased lymphocyte infiltration with no demyelinated surface area in the lumbar spinal cord of fluvoxamine-treated, in comparison to PBS-treated EAE rats. Finally, immunofluorescent analysis clearly showed decrease in number of activated astrocytes (GFPA positive cells) and increase in area of mature oligodendrocyte (MBP positive cells) in fluvoxamine treated EAE groups, in comparison to PBS treated EAE rat.

In conclusion, for the first time, our results indicated a positive impact of fluvoxamine on proliferation and differentiation of cultured ENSCs. Moreovere, high potential of fluvoxamine in EAE improvment was confirmed by indication its anti-inflammatory and oligodendrogensis activies. Our data suggest that fluvoxamine could be one of the antidepression drugs in MS patient with anti-inflammatory and remyelination effects, which needs further clinical studies.

Biography:

Shivam Bansal is presently an undergraduate (final year) student at the premier institute, AIIMS, New Delhi. He is a topper in the institute and has been awarded medal and certificate for obtaining highest marks in the subject of Biochemistry and Microbiology. Apart from academic work, he is active in research in the Dept. of Neurology under Prof. Achal Srivastava (well acclaimed in the field of headache, ataxia, intractable epilepsies and spinal cord disorders) as the guide. The above mentioned research was also selected for oral presentation at annual convention of Aiimsonians of America (AoA) at Daytona Beach, Florida. 

Abstract:

Background:

Studies suggest a degree of autonomic dysfunction which gets implicated in pathophysiology of migraine but none has ever commented on differences among ictal and interictal (headache free) period of migraine. Therefore this pilot study aims at assessing and comparing autonomic function during ictal and interictal period.

Methods and Materials:

Patients with migraine according to ICHD 3^rd edition β version criteria were recruited for the study. Tests of sympathetic function (beat to beat blood pressure changes in Head-Up-Tilt test) and parasympathetic function (heart rate responses to Deep Breathing and Valsalva Manoeuvre) were performed, each during ictal and interictal period. The results of the ictal period were then compared with that of interictal period.

Results:

Ten patients [Eight female (80%), 20-58 years, mean 34.6] were studied. Nine patients (90%) showed Expiration:Inspiration [E:I] ratio {Ratio of maximum RR interval during expiration phase with minimum RR interval during inspiration phase} in Deep Breathing test below 1.24 and four patients (40%) showed 30:15 ratio {Ratio of RR interval during 30^th heart beat with that during 15^th heart beat} in Head-Up-Tilt test below 1.04, thus indicating significantly higher vagal response. These results were in ictal period. All patients exhibited normal parasympathetic response during interictal period and intact sympathetic function during both ictal and interictal periods.

Conclusion:

Subjects with migraine had vagal hyperactivity and intact sympathetic function during ictal period, whereas no abnormality was found during headache free period. This study provides newer insight into the pathophysiology of a migraine attack which may lead to further studies with new therapeutic approaches.

Biography:

Son CG graduated Oriental Medical Collage of Daejeon University, and then  had finished a clinical training course for internal medicine specialist in Daejeon Oriental Hospital, and PhD degree in Daejeon University. He had studies in oncology branch, NCI, NIH, USA as a post-doctoral fellow from 2002 to 2004. Currently he is a professor and director of Institute of Traditional Medicine & Science, Daejeon University. He has focused his research on a broad range of Traditional Oriental medicine in both laboratory and clinical studies.

Abstract:

We evaluated the neuropharmacological effects of Gongjin-Dan (GJD) on the memory impairment caused by scopolamine injection. BALB/c mice were orally treated with GJD (100, 200, or 400 mg/kg, daily) or tacrine (THA, 10 mg/kg) for 10 days, and scopolamine (2 mg/kg) was injected intraperitoneally. The radial arm maze and passive avoidance tests were performed to evaluate the animal’s learning and memory. Scopolamine increased the time to complete the task, the number of total errors (reference and working memory error) in the radial arm maze task, and the latency time in the passive avoidance test, which were significantly ameliorated by treatment with GJD. The GJD treatment also ameliorated the scopolamine-induced hyperactivation of acetylcholinesterase activity, and suppression of the expression of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and their receptors in the hippocampus. These effects of GJD were supported by both the doublecortin (DCX)-positive staining, which was used to detect hippocampal neurogenesis, and Nissl staining, which was used as a measure of hippocampal atrophy. These findings strongly suggest that GJD exerts a potent anti-amnesic effect, and its underlying mechanism might involve the modulation of cholinergic activity.

Biography:

Binna Kim is a PhD candidate in the Interdisciplinary Program in Brain Science at Seoul National University, South Korea. She is also a researcher at Ewha Brain Institue. She received her BS in chemistry and BA in psychology from the SNU in 2011. Binna Kim was granted Global PhD Fellowship scholarship from National Research Foundation of Korea, and participated in several projects as well. Her current research interests include cognitive and social neuroscience.

Abstract:

Recent advance in computational analysis of multimodal neuroimaging using machine learning algorithms may enable early diagnosis of central nervous system diseases and predict the subsequent prognosis with high accuracy. In the current study, disaster survivors who were diagnosed with posttraumatic stress disorder (PTSD) in the early aftermath of trauma and healthy individuals who were not exposed to trauma were followed up as the trauma-exposed and trauma-unexposed groups prospectively. We assessed the multimodal characteristics of the fear circuitry’s brain regions including the amygdala, ventral prefrontal cortex, and hippocampus with volume, connection density, connection cost, tract strength, and network efficiency as variables associated with brain regions. Using a classification approach with multimodal neuroimaging data for an analysis, features of particular subset brain regions - the amygdala, ventral prefrontal cortex, hippocampus, insula, and thalamus - were identified to best characterize those of trauma-exposed group. We found that amygdalar volumes and the tract strength of its connections in combination with the insula and with the thalamus each were robust brain classifiers for the trauma-exposed group during an early stage of post-trauma when most of the survivors still meet the diagnostic criteria for PTSD. In contrast, the tract strength of the amygdala-ventral prefrontal cortex connection was a differentiating feature of the trauma-exposed group from that of the trauma-unexposed group during the recovery period from PTSD. These results suggest that the use of multimodal imaging analysis may applied as a competent and efficient tool in PTSD risk prediction.

Biography:

Shivam Bansal is presently an undergraduate (final year) student at the premier institute, AIIMS, New Delhi. He is a topper in the institute and has been awarded medal and certificate for obtaining highest marks in the subject of Biochemistry and Microbiology. Apart from academic work, he is active in research in the Dept. of Neurology under Prof. Achal Srivastava (well acclaimed in the field of headache, ataxia, intractable epilepsies and spinal cord disorders) as the guide. The above mentioned research was also selected for oral presentation at annual convention of Aiimsonians of America (AoA) at Daytona Beach, Florida. 

Abstract:

Background:

Studies suggest a degree of autonomic dysfunction which gets implicated in pathophysiology of migraine but none has ever commented on differences among ictal and interictal (headache free) period of migraine. Therefore this pilot study aims at assessing and comparing autonomic function during ictal and interictal period.

Methods and Materials:

Patients with migraine according to ICHD 3^rd edition β version criteria were recruited for the study. Tests of sympathetic function (beat to beat blood pressure changes in Head-Up-Tilt test) and parasympathetic function (heart rate responses to Deep Breathing and Valsalva Manoeuvre) were performed, each during ictal and interictal period. The results of the ictal period were then compared with that of interictal period.

Results:

Ten patients [Eight female (80%), 20-58 years, mean 34.6] were studied. Nine patients (90%) showed Expiration:Inspiration [E:I] ratio {Ratio of maximum RR interval during expiration phase with minimum RR interval during inspiration phase} in Deep Breathing test below 1.24 and four patients (40%) showed 30:15 ratio {Ratio of RR interval during 30^th heart beat with that during 15^th heart beat} in Head-Up-Tilt test below 1.04, thus indicating significantly higher vagal response. These results were in ictal period. All patients exhibited normal parasympathetic response during interictal period and intact sympathetic function during both ictal and interictal periods.

Conclusion:

Subjects with migraine had vagal hyperactivity and intact sympathetic function during ictal period, whereas no abnormality was found during headache free period. This study provides newer insight into the pathophysiology of a migraine attack which may lead to further studies with new therapeutic approaches.

Biography:

Borovok Natalya has completed her PhD at the age of 34 years from Institute of Chemical Physics, Russian Academy of Sciences, Moscow, Russia and postdoctoral studies from Tel-Aviv University, Department of Biochemistry, Israel. She is the senior researcher of the Department of  Biochemistry and Molecular Biology, Tel-Aviv University . She has published more than 30 papers in reputed scientific journals.

Abstract:

Background: Serine/threonine kinase AKT/PKB plays a fundamental role in a wide variety of neuronal functions, including neuronal cell development, axonal growth and synaptic plasticity. Recently, a further downstream mechanism of AKT involvement in long-term depression (LTD) prevention and late phase long-term potentiation (LTP) has been revealed. However, no solid knowledge has been accumulated regarding the downstream effectors mediating AKT’s effects on early phase LTP (eLTP). Aim: elucidating of the role of AKT in eLTP regulation. Results: Using different regimes for application of the AKT inhibitor A6730 (30 min drug exposure before high frequency stimulation (HFS), drug for 30 min before and 20 min after HFS, drug for 20 min 30 min after HFS), to acute hippocampal slices trained with the HFS paradigm, we observed that AKT regulates LTP induction and expression without affecting its maintenance. Further, we delivered an AKT activator to combine with inhibitors of various signaling pathways to prevent AKT activation-induced effect on LTP and to characterize a potential downstream mechanism of LTP regulation. Unexpectedly, SC79 (activator of AKT), which also prevents AKT translocation to the plasma membrane, induced a significant decrease in basal synaptic activity and in expression of LTP. Conclusions: 1) translocation of AKT towards the plasma membrane is necessary for regulation of synaptic activity and LTP. 2) AKT related LTP expression is not dependent on downstream cytosolic factors, but is mediated via direct effects of AKT on post-synaptic density components and glutamate receptors.