Day 1 :
Keynote Forum
Jun Zhu
University of South Carolina, Columbia, SC
Keynote: Allosteric modulatory effects on HIV-1 Tat protein-induced inhibition of human dopamine transporter function
Time : 09:35-10:15
Biography:
Dr. Zhu’s research aims toward finding solutions to a newly recognized challenge in treatment for HIV-associated neurocognitive disorders (HANDs). About one-half of HIV-1-positive individuals suffer from HAND, which dramatically affects memory, learning, decision-making, planning and overall quality of life. Cocaine has been shown to exacerbate the severity of HAND. HAND is associated with HIV-1 viral proteins, which are present in the brain of HIV-1-infected patients. HIV-1 transactivator of transcription (Tat) protein--an HIV regulatory protein--is thought to inhibit neuronal communication by acting directly on the human dopamine transporter, a membrane protein in the brain responsible for pumping the dopamine back into the cytosol and terminating dopamine signaling during neurotransmission. Dr. Zhu’s project is to investigate how cocaine and Tat work to create binders that derail neuronal communication in the brain. The ultimate goal is to develop neuroprotective drugs and help HIV patients recover their neurological function.
Abstract:
The inducible HIV-1 Tat transgenic (iTat) mouse model recapitulates many aspects of neurocognitive impairments observed in HIV infected individuals. Tat and cocaine synergistically increase synaptic dopamine (DA) levels by directly inhibiting DA transporter (DAT) activity, ultimately leading to dopaminergic neuron damage. This study determined allosteric modulatory effects of SRI-30827 on HIV-1 Tat protein-mediated regulation of human DAT and cocaine condition place preference (CPP) in iTat mice. Results show that SRI-30827 attenuated Tat-induced inhibition of [3H]DA uptake and [3H]WIN35,428 binding in PC12 cells expressing human DAT. After a 7-d doxycycline (Dox) treatment, HPLC analysis revealed that DA content in the prefrontal cortex (PFC) and nucleus accumbens (NAc) of iTat-Tg mice were increased by 92% and 37%, respectively, compared to control mice. Consistently, DA/DOPAC in the PFC and NAc of iTat-Tg mice was increased by 44% and 26%, respectively. We performed the patch clamp recording to measure medium spine neurons (MSN) firing in brain NAc slices of iTat mice in the presence of DA and cocaine. Results show that that action potential frequency of NAc shell MSN was significantly increased in iTat mice compared to control mice. Further, action potential frequency of NAc shell neurons was decreased in response to 5 μM cocaine, and further decreased when cocaine and 5 μM were applied together, which were completely attenuated in iTat mice. Finally, we found that ICV infusion of SRI-30827, a novel allosteric modulator, partially attenuated the potentiated cocaine-CPP in iTat mice. These findings suggest the hypothesis that Tat potentiates cocaine rewarding effect and allostericmodulator has potential for treatment of Tat-induced drug reward.
Keynote Forum
Ming-Chao Huang
Taipei Veterans General Hospital, Taipei, Taiwan
Keynote: Leptin is essential for spinal microglia activation and the development of neuropathic pain after preganglionic cervical root avulsion
Time : 10:15-10:55
Biography:
Ming-Chao Huang was born in 1958, in Taipei, Taiwan. He obtained MD degree from Taipei Medical University, Taiwan, in 1984. He got his PhD degree from Tokyo Women’s Medical University, Japan, in 1996. He is a neurosurgeon and is currently the division Chief of Department of Neurosurgery, Taipei Veterans General Hospital, Taipei, Taiwan. He is also the Associate Professor of Taipei Medical University and Central Taiwan Technological University. His clinical specialty includes spinal surgery (including degeneration and trauma), peripheral nerve surgery (including tumor surgery and nerve repair), and brain tumor surgery. His research interests are nerve root injury (including basic mechanism and surgical repair), neuropathic pain (including basic study and treatment), and brain tumor (including medical and surgical treatment).
Abstract:
Preganglionic cervical root avulsion (PCRA) affects both the peripheral and central nervous systems and is often associated with neuropathic pain. Unlike peripheral nerve injuries (PNI), central lesions caused by disruption of cervical roots from the spinal cord following PCRA contribute to the generation of neuropathic pain. Leptin is involved in the development of neuropathic pain after PNI by affecting neurons. However, whether leptin is involved in microglial activation leading to neuropathic pain after PCRA is unknown. In this studies, the preganglionic avulsion of the left 6th-8th cervical roots was performed in C57B/6J mice and leptin-deficient mice. A leptin antagonist or leptin was administered to C57B/6J mice and leptin-deficient mice after injury, respectively. The expression pattern of spinal microglia was examined by immunofluorescent staining. Von Frey filaments were used to test pain sensitivity. Our data showed that leptin is essential for the development of neuropathic pain after PCRA. Allodynia was absent in the leptin-deficient mice and the mice administered the leptin antagonist. We also found that leptin deficiency or the administration of its antagonist inhibited the development of microgliosis, the expression of CD86 and iNOS, and Wallerian degeneration in the spinal cord. Moreover, the administration of exogenous leptin to leptin-deficient mice reversed these effects. We concluded that leptin is involved in the proliferation and activation of microglia, which in turn enhances the development of neuropathic pain. Blocking the effects of leptin might be a target for the treatment of neuropathic pain after PCRA.
Keynote Forum
Wen-Hai Chou
Neuropsychiatric Research, National Health Research Institutes, Taiwan
Keynote: PKCε-ATF2 signaling in ischemia-induced Neurodegeneration
Time : 11:15-11:55
Biography:
Dr. Wen-Hai Chou received his PhD from Department of Molecular Medicine, University of Texas Health Science Center, San Antonio, and post-doctoral studies from University of California, San Francisco. He is an Assistant Investigator of National Health Research Institutes, Taiwan. He has published more than 22 papers in reputed journals including Neuron, Journal of Clinical Investigation, Journal of Neuroscience, and Journal of Biological Chemistry. He was elected as a Fellow of the American Heart Association (F.A.H.A.) for making major and productive contributions in cardiovascular basic sciences in 2011
Abstract:
Cardiac arrest continues to be the leading cause of death worldwide. Global cerebral ischemia that accompanies cardiac arrest is one of the major causes of morbidity and mortality. Out of many therapeutic approaches investigated, one of them is ischemic preconditioning, which is sufficient to protect brain tissues from subsequent lethal ischemic insult. PKCε peptide activator administered before, but not after, ischemia mediates preconditioning and confers neuroprotection. However, the use of preconditioning as a therapeutic approach has not become standard clinical practice because the occurrence of cardiac arrest and cerebral ischemia is sudden and unpredictable. Thus, post-ischemic therapeutic targets have to be unraveled. The beneficial effects of PKCε peptide activators in ischemic preconditioning stimulate interests in understanding the molecular and cellular actions of PKCε after global cerebral ischemia. A detailed understanding of PKCε signaling pathways requires identification of its downstream targets. This study is to determine the downstream mediators of PKCε, so that novel therapeutic targets can be developed. We found that PKCε mediated the phosphorylation of Activating transcription factor 2 (ATF2) at Threonine 52 in the hippocampus. ATF2 is a member of the activator protein 1 (AP1) transcription factor superfamily regulating normal growth and development as well as response to cellular stress. In response to global cerebral ischemia, PKCε expression was gradually decreased. This resulted in leakage of nuclear ATF2 to the mitochondria, and subsequent ischemia-induced neurodegeneration (Fig. 1). This study not only provides the first insight into the neuronal cell death regulated by PKCε and ATF2, but also establishes a strong base to develop new classes of therapeutic molecules to inhibit the leakage of ATF2 and reduce brain injury after cardiac arrest.
- Neurology | Spine and Spinal Disorders | Pediatric Neurology | Clinical Neurology | Dementia | Parkinsons | Neurosurgery | Diagnosis and Imaging Techniques | Pharmaceuticals and Therapies | Case reports
Session Introduction
Shang-Hsun Yang
Department of Physiology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
Title: A miracle (miR-196a) in the fight against Huntington Disease
Biography:
Dr. Shang-Hsun Yang is the Associate Professor in Department of Physiology, at National Cheng Kung University, Tainan, Taiwan. He received his B.Sc. degree at National Chung Hsing University in 1998, M.Sc. degree at National Taiwan University in 2000 and Ph.D. degree at Emory University, USA, in 2008. He has developed his own research career at NCKU since 2009. His research interests focus on the regulation of microRNAs on HD, and tries to understand the regulatory mechanisms and potentially therapeutic directions for this neurodegenerative disease. Additionally, he also attempts to expand his research fields to other neurodegenerative diseases, and wishes to demonstrate the relationship between specific microRNAs and neurodegenerative diseases
Abstract:
Huntington’s disease (HD) is a genetic disease, and caused by a mutation in Huntingtin gene, leading to neuropathological symptoms. To date, there is no effective medicine for HD. Based on previous studies, transcriptional regulation is impaired during the progression of HD, and regulation of microRNA(miRNA) is one of affected mechanisms. Since HD leads to dysfunction of gene regulation and one miRNA could target to multiple pathways, it suggests miRNA could be one potential treatment for HD. In my laboratory, we identified one potential miRNA, miR-196a, from HD transgenic monkeys, and found the neuroprotective effects of miR-196a on HD in cell, transgenic mouse and HD patient-derived induced pluripotent stem cell models. miR-196a could not only improve molecular, neuropathological and behavioral phenotypes in transgenic mouse models, but also suppress pathological aggregates in neurons derived from HD patients. Furthermore, we also investigate molecular mechanisms of miR-196a, and show miR-196a could enhance cellular morphology, intracellular transport, synaptic plasticity, neuronal activity, learning and memory both in vitro and in vivo. In addition, miR-196a could work through binding to 3’ untranslated region of RAN binding protein 10 (RANBP10) to suppress the protein expression, further enhancing the assembly of β-tubulin. Most importantly, overexpression of RANBP10 led to worse neuronal morphology and severer pathological phenotypes in the HD transgenic mouse model, suggesting that miR-196a enhances neuronal morphology through suppressing RANBP10 to provide neuroprotection in HD. These results suggest the important role of miR-196a on HD, and might provide a new insight of therapeutical strategy for HD
Eyleen GOH
Duke-NUS Medical School in Singapore
Title: Choline as a Nutraceutical for Treating Neurodevelopmental Disorder: Rett syndrome
Biography:
Asst professor Eyleen Goh is a senior research scientist at the National Neuroscience Institute and an assistant professor with the Duke-NUS Medical School in Singapore. Her research laboratory aims to understand the fundamentals of brain development and functions, and to search for possible intervention strategies for neurodevelopmental and neurodengenerative disorders. Besides the usual pharmaceutical approach, they are also exploring nutraceutical approach for the treatment of these brain disorders. Using cell cultures, animal models and human patient-derived cells, the lab is investigating the effects of micronutrients on neuronal development, circuitry and cognitive functions, to understand how micronutrients or the transport of these micronutrients affect brain functions and to determine if micronutrients can be used as treatment for neurological disorders.
Abstract:
Rett syndrome (RTT) is a postnatal neurodevelopmental disorder that primarily affects girls, with 95% of RTT cases resulting from mutations in the methyl-CpG-binding protein 2 (MECP2) gene. To model RTT in vitro, a short hairpin RNA was used to knockdown the expression of MeCP2 in primary neurons. Abnormalities in the cholinergic system have been shown to be associated with the disorder. We found choline supplementation to MeCP2-knockdown neurons increased their soma sizes, and the complexity of their dendritic arbors. Through the use of specific inhibitors targeting each of the known physiological pathways of choline, synthesis of phosphatidylcholine from choline was found to be the most important pathway in bringing about the changes seen in choline-supplemented MeCP2-knockdown neurons. Rescue of the morphological defects could lead to enhanced neurotransmission, as suggested by an observed trend of increased expression of selected synaptic proteins in choline-supplemented cells, and differences in dendritic spine density and shape between wild type and Mecp2-knockout mice, with choline or vehicle supplementation. In addition, choline supplementation to cultured hippocampal neurons restored mini excitatory postsynaptic current frequencies in MeCP2-knockdown cells to control levels, while the amplitude was unchanged. Choline treatment to MeCP2-knockout mice also rescued deficits in motor coordination, anxiety-like behaviour, and social interaction. Taken together, these data reveal a role of choline in modulating neuronal plasticity, possibly leading to behavioural changes, and hence, a potential for using choline to treat RTT.
Ashutosh Kumar
All India Institute of Medical Sciences. India
Title: Induction - reversal modeling of psychiatric disorders by functional manipulation of habenular pathways in zebrafish
Biography:
Dr. Ashutosh Kumar is the coordinator for the Etiologically Elusive Disorders Research Network (EEDRN), New Delhi, India: a research group which organizes collaborative research on difficult to treat human diseases for which etiology is exactly not known. His research group has recently made many noticeable publications in international peer reviewed journals. He is a medical post graduate from All India Institute of Medical Sciences (AIIMS), New Delhi, has been faculty in Anatomy at Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Karaikal, Pondicherry. He is currently working as the research associate at Laboratory of Molecular and Cell Biology, Department of Anatomy, AIIMS, New Delhi.
Abstract:
The etiomechanism of psychiatric disorders is still little understood. Optogenetically induced changes in neural networks and consequent change of behaviour in transgenic animals has provided a novel opportunity to develop animal models of various psychiatric disorders. We hereby propose zebrafish as a model organism based on the premise of its intricate analogy with mammalian brain. The habenula is an evolutionarily conserved bilateral structure located at the interface of diencephalon, basal nuclei and brainstem working as a gateway between cortical-subcortical and brainstem structures. Multiple studies have suggested master role of habenula in control of adaptive behaviour through regulation of brainstem aminergic nuclei. It is thought to function as a switchboard for regulating emotional behaviour in conditions facing survival challenges. The dysregulation of the emotional behaviour has been at the base of psychiatric disorders, and a functional manipulation of specific habenular nuclei using optogenetics combined with incremental levels of stress challenge may prove to be a basic model for the genesis of psychiatric disorders. Conversely, reversing the manipulation, scaling down stress levels, and providing enriched environment may ease psychiatric symptoms. The present article has proposed a hypothesis on the development of a basic zebrafish model for the psychiatric disorders based on this concept. Such a model may be of great help in understanding the common mechanism involved in genesis, progression of various psychiatric disorders. The article has also elaborated on the operational mechanisms and validity of the methodology, and has suggested an experimental design for the proposed study model.
- Young Research Forum
Session Introduction
Chun-Wei Hsu
University of Plymouth
Title: The effect of mental countermeasures on fMRI-based concealed information tests
Biography:
Chun-Wei Hsu is doing her Ph.D. in Psychology at University of Plymouth since April 2014. She went to undergraduate school at National Taiwan University, and double majored in life science and psychology within four years (Sep. 2007 – Jun. 2011). Later, she completed a master’s degree in Cognitive Neuroscience and Human Neuroimaging at University of Sheffield (Se. 2012 – Aug. 2013). Currently, her Ph.D. project is to explore the cognitive mechanisms underlying deception through creativity and neuroscience. Chun-Wei is interested in how people conduct high-level cognition in complex social interaction and how people evaluate expect the pay-offs and take action during the decision-making process. Ideal interaction requires people to simulate others' perspectives and shape their behaviors, which is of great interest to her. Human neuroimaging methods with fMRI or EEG are the approach she wants to use to answer my research questions
Abstract:
Concealed information paradigms (CITs) have been developed to determine if an individual is familiar with a certain piece of information such as a crime-related item. The main logic of CITs is that recognition of an item of interest (probe) will generate a differential response, compared to suitable control items (irrelevants), that can be detected by monitoring behavioral, psychophysiological, or neural variables.
An important issue is an extent to which countermeasures used by suspects can reduce the accuracy of the CIT. Recent work has focused on neural variables measured with functional magnetic resonance imaging (fMRI) because at first sight, such variables may seem more resistant to countermeasures than more peripheral variables. Previous work has shown that hybrid physical and mental countermeasures can decrease the accuracy of fMRI-based CITs, but questions remain as to whether purely mental countermeasures can do so as well. Existing evidence shows that attentional and memory strategies can decrease the accuracy with which one can use fMRI to detect successful recognition in standard face recognition tasks.
The aim of this fMRI study was to determine if such mental countermeasures are effective also with standard CITs. Participants (N=20) were tested under three conditions: no knowledge, concealed knowledge, and countermeasures. Results based on regions of interest defined in previous CIT studies showed that the area under the curve (AUC) for discriminating no knowledge and concealed knowledge cases with multi-voxel pattern analyses was 0.86 without countermeasures. Critically, memory and attentional countermeasures significantly reduced the AUC to 0.74.
These results indicate that purely mental countermeasures can reduce the accuracy of fMRI-based CITs, even without extensive training of participants.
Amira Elaalem
ALNeelain university
Title: Relative risk factors of Bell’s palsy among Sudanese patients in Khartoum state 2016
Biography:
Amira Elaalem is 27 years old female, completed her master degree in Neurology physiotherapy at Alneelain University (Sudan). Studied physiotherapy BSC at Alneelain University Faculty of Medicine and health science, and now studying in my last year in MBBS program. She finished Diploma degree at research methodology and ethics held at Alneelain University and collaboration with Maryland University. Her research publication is under process.
Abstract:
Bells palsy is the idiopathic seventh cranial nerve palsy. It is the most common cause of abrupt onset of unilateral facial weakness. The natural history of Bell’s palsy is encouraging for most of the patients since total recovery of facial function is expected, nevertheless additional long term poor outcomes occur in minority of them and can be devastating. Currently, no cause for Bell’s palsy has been identified in the literature, but in Sudan there were very few information can be retrieved.
Hence the overall objective of the study was to assess the potential relative risk factors of Bell’s palsy in Sudanese patients.
Methodology
This is analytic case control multicenter based study. Conducted in Khartoum state physiotherapy centers (three in hospital and seven in private sectors) July - November 2016. The sample size was 70 cases of Bell’s palsy and 140 controls from the same sample area. The cases that fulfilled the inclusion criteria were collected by a method of total coverage during the working hours. Well constructed questionnaires were filled during the interview by a trained physiotherapist. The collected data was then analyzed using SPSS software program, version 20.
Results
The result showed the statistically significant factors (p value < 0.05) are: recurrence of Bell’s palsy ten times more in affected patients, the hereditary factor 2.5 times more in affected patients. In contrast to the other factors were non statistical significance (p value > 0.05) are: recent vaccination, pregnancy, diabetes, hypertension, chronic diseases, immunosuppressive drugs, smoking and alcohol and.
Conclusion
The study concluded that, statistical significant factors are frequency of recurrence of Bell’s palsy, genetic susceptibility. The rest of risk factors were statistical non significant.
We recommend more studies deserve to be done to determine the type of inheritance in Sudan and study the cause of recurrence
Biography:
Arunkumar Prasad is the last year student in Taishan Medical University, China. He is the President of the Student Oragnisation in the field of Academics and other activities in TSMU. He was one of the speaker at the Euro Brain Injury 2017 held in London, UK. He is currently working as a young researcher and studying under his Professor Baoliang Sun (Neurologist, PhD, Dean of TSMU).
Abstract:
Recent studies suggest that CNS lymphatic drainage pathway to extracranial lymph compartments may play an important role in the removal of substances in the brain and cerebrospinal fluid (CSF). After the onset of subarachnoid hemorrhage (SAH), large amount of macromolecular substances, such as cellular lysates, proteins, peptides, were accumulated in the brain tissue and CSF, which contribute to cerebral vasospasm and cerebral injury. The present experiment was carried out to investigate the possible role of cerebral lymphatic drainage pathway in the development of cerebral vasospasm and related cerebral injury and the influence of Ginkgo biloba extract. Wistar rats were used in the experiment and animals were divided into different groups. SAH models were replicated by double cisternal injection of autologous arterial hemolysate. In some animals the main cerebral lymphatic drainage way out being blocked (cerebral lymphatic blockade, CLB). Two different constituents, Ginkgolides and Ginkgo flavone, were given as interventions. It was found that SAH reduced the drainage of Evans blue-labeled albumin (EBA) from the brain to the olfactory bulbs, cervical lymph nodes and abdominal paraaortic lymph nodes. A kinetic analysis of 125I-labeled human serum albumin (125I-HSA), a cerebrospinal fluid (CSF) tracer, showed that the clearance rate of macromolecules in the CSF was significantly reduced after SAH. Furthermore, SAH reduced the diameters of basilar artery (BA) and increased thickness of BA. Prominent cerebral injury was found after induction of SAH. The spasm of BA and cerebral injury were partially antagonized by Ginkgolides and Ginkgo flavone. It was concluded that cerebral lymphatic drainage pathway exerts intrinsic protective effects against cerebral vasospasm and cerebral injury by removal of macromolecular substances in the brain and subarachnoid spaces. Ginkgolides and Ginkgo flavone may alleviate the exacerbated cerebral vasospasm and cerebral injury following SAH by CLB.
Issa O. Yusuf
Interdisciplinary Neuroscience Academia Sinica, Taiwan
Title: Fibroblast Growth Factor 9 Suppresses cell death through ERK signalling in Huntington’s disease
Biography:
Yusuf Issa Olakunle is a PhD student in Taiwan International Graduate Program (TIGP) Academia Sinica of the Neuroscience, at National Cheng Kung University (NCKU). He obtained his B.Sc. degree in Physiology from Ahmadu Bello University, Zaria, Nigeria, in 2010, and M.S.c degree in Physiology from the University of Ibadan, Nigeria, in 2014. He currently conducts his research works in Dr. Yang’s laboratory in the Department of Physiology, NCKU, and demonstrates on the therapeutic roles of FGF9 and miR-196a in Huntington’s disease (HD).
Abstract:
Statement of Problem: Huntington’s disease (HD) is a heritable neurodegenerative disorder characterized by selective and progressive damage of medium spiny neurons in the striatum, and there is no cure for HD to date. A type of fibroblast growth factor (FGF), FGF9, has been reported to play prosurvival roles, in other neurodegenerative diseases, such as Parkinson’s disease and Alzheimer’s disease. With many similarities in the cellular and pathological mechanisms that eventually cause cell death in neurodegenerative diseases, we hypothesize that FGF9 might provide neuroprotective functions in HD. Methods and Findings: Here, we used STHdhQ7/Q7 (WT) and STHdhQ111/Q111 (HD) striatal knock-in cell lines as our models, and examined the neuroprotective effects of FGF9 on HD. Employing MTT and PI staining assays to determine cell proliferation and survival respectively, we found that FGF9 enhanced cell proliferation and also increased cell survival under a starvation stress condition. In addition, we observed that FGF9 significantly upregulated FGF signalling through ERK1/2, Akt, JNK, and mTOR pathways, and increased neurotrophic factor (GDNF) and anti-apoptotic BcL-xL proteins in HD cells. Especially, ERK pathway plays a critical role in the effects of FGF9 on cell survival and GDNF regulation. Conclusion and Significance: These results not only show the neuroprotective effects of FGF9, but also clarify the critical mechanisms in HD cells, further providing therapeutic potential of FGF9 in HD.