Day 1 :
University of South Carolina, Columbia, SC
Keynote: Allosteric modulatory effects on HIV-1 Tat protein-induced inhibition of human dopamine transporter function
Time : 10:00-10:45
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.
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.
National Neuroscience Institute, Singapore
Time : 10:45-11:30
Kah-Leong Lim obtained his Ph.D. from the Singapore Institute of Molecular & Cell Biology in 1999. Thereafter, he did his postdoctoral training at the Department of Pathology in Harvard Medical School (2000-2001), and subsequently at the Department of Neurology in Johns Hopkins University School of Medicine (2001-2002), where he worked on the topic of Parkinson’s disease with Professor Ted Dawson. Dr. Lim is currently the Deputy Director of Research at the National Neuroscience Institute of Singapore and Director of Basic and Translational Research in the Singhealth Duke-NUS Neuroscience Academic Clinical Program. He is a member of the National Grant Review Panel (NMRC) and a regular reviewer of international grants including applications from the Welcome Trust and Medical Research Council (UK). Dr. Lim is an editor for PLoS One and Frontiers in Cellular Neuroscience and a guest editor for PLoS Genetics. His research focuses on therapeutic development for Parkinson’s disease.
Parkinson disease (PD) is a prevalent neurodegenerative disease affecting millions of predominantly elderly individuals worldwide. Despite intensive efforts devoted to drug discovery, the disease remains incurable. Compounding this problem is the current lack of a truly representative mammalian model of PD. Interestingly; the Drosophila has emerged as a good system to model the salient features of the disease, including dopaminergic (DA) neurodegeneration and associated locomotion defects. Taking advantage of this and also the utility of the Drosophila as a tool for drug discovery, we have uncovered several neuroprotective compounds and associated targets. These include AMP Kinase (AMPK) activators that are relevant in human PD cases. Our results support the use of Drosophila PD model as an intermediate in vivo host for phenotype-based drug screening. Because PD involves the degeneration of neurons in a rather circumscribed region in the brain, neurorestorative therapy via cell replacement represents another strategy to treat the disease. Here, we have exploited the induced pluripotent stem cell (iPS) technology to derive transgene integration- and feeder-free iPS from cells lining the human umbilical cord, an immunoprivileged organ that mediates interactions across the feto-maternal interface. Collectively designated as CLiPS (Cord Lining-derived iPS), we demonstrated that CLiPS-derived DA neuronal precursors transplanted into an immunocompetent 6-hydroxydopamine mouse model of PD not only survived but also differentiated into mature DA neurons in the absence of pharmacological immunosuppression. Further, the engrafted mice showed functional motor recovery and restoration of dopamine level (illuminated via PET imaging). These results position CLiPS as a promising source of donor cells for allogeneic cell replacement therapy for PD (Supported by NMRC-TCR).
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 : 12:00-12:45
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).
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.
- Neurology | Spine and Spinal Disorders | Pediatric Neurology | Clinical Neurology | Dementia | Parkinsons | Neurosurgery | Diagnosis and Imaging Techniques | Pharmaceuticals and Therapies | Case reports
Duke-NUS Medical School in Singapore
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.
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.
University of Plymouth
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
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 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.
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.
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.
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.
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
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).
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.
All India Institute of Medical Sciences. India
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.
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.
Baba Farid University of Health Sciences, India
Mr. Varun Vikas Vij has done M pharmacy in Pharmacology and pursuing PhD from Baba Farid University of Health Sciences Faridkot Punjab India and currently working as a Pharmacy Executive in Dayanand Medical College and Hospital Ludhiana Punjab India. Mr. Vij has 11 years of experience in pharmaceutical industry (9 years in Pharmaceutical marketing and 2 years in Hospital pharmacy). He has 2 International publications. He has keen interest in Neuro Pharmacology.
Neuropathic pain (NP) is defined as pain associated with damage or permanent alteration of the peripheral or central nervous system. Current drug treatment for the management of neuropathic pain associated with various adverse effects. The present study was designed to investigate the combined effect of acamprosate and baclofen in experimental model of peripheral Neuropathic pain in wistar rats. Material and Methods: Neuropathic pain was induced by chronic constriction injured (cci) of sciatic nerve in rats. A camprosate (100 and 200 mg/kg p.o) and baclofen (10 and 20 mg/kg p.o) was given in different groups for 14 days starting on 7th day post sciatic nerve ligation. Further combination of acamprosate(100 mg/kg p.o) and baclofen (10 mg/kg p.o) was also given to one group. On 1th, 3rd, 7th, 14thand 21stday behavioral parameters like mechanical allodynia and thermal hyperalgesia were assessed. Then animals were sacrificed on 22nd day and biochemical parameters (gsh, lpo, catalase, nitrite, sod) were assessed. Results: ligation of sciatic nerve significantly induced mechanical allodynia and thermal hyperalgesia with increase in oxidative stress (increase in lpo and nitrite) and decline of anti-oxidant enzyme levels (catalase, sod, gsh) in sciatic nerve homogenate. A camprosate (100 and 200 mg/kg p.o) and baclofen (10and 20 mg/kg p.o) attenuated all the behavioural and biochemical parameters alone and/or combination.
Nancy Brassard is a professor-researcher at the ENA University of Quebec teaching psychology, work, and mental health. Recently, completed superior studies in neuroscience to understand better the brain, its functions and those pathologies related like depression and FTD. Scientist with a strong family history of FTD.
At the beginning of Nancy Brassard mother’s disease, felt that I have to do something to help or to stop that! I began at this time to work intensively on what I am calling: The Quest! I asked my family members to participate with my mother and me at the study. I collected a lot of datas, made interviews and I built the whole family symptoms and history. This “Quest” led me to the Aging and memory center in May 2016, as a visiting scholar and to contribute slightly in the laboratory activities of Dr. Rankin. In last August, I had the honor of being invited by Dr. Bruce Miller to speak at the opening conference of Tau consortium in Denver. The title for my presentation was: Patient advocacy: A family story. At that time, I perceived the urgent need to help and support people dealing with a familial reality of FTD. This is unique!
I have initiated the past two years, studying in medicine and neuroscience, to better understand degenerative brain diseases especially, the stages, the onset of symptoms and the link with other variables such as, personality traits or lifestyle. I know that I can contribute to your event in many ways. First, I am teaching at the University since 12 years. I can contribute by my undeniable teaching skills, my openness and my strong ability to work in team. I have a strong research expertise and my scientific research skills are recognized by the scientific community. Second, being myself at risk of a brain disease, and as the President-founder of a non-profit Society, I am a great “Ambassador” to contribute with the researchers in the field in participating to their projects or to answer their questions, and share with them the importance of finding a cure for the families. I am hopeful, in a positive mind and I feel like if I have a mission. As a researcher, and especially as a daughter, and most of all, as a mother, I am in a Quest! Willing to participate or collaborate to find a cure or treatments and help people to deal with the disease and conciliate, understand and live with those realities. I want to be an example to show them that it is possible. I did it, I am doing it and I will continue to pursuit this Quest with passion, dedication and compassion.
Bangladesh is a small densely populated country facing problems of communicable and non-communicable diseases. By the enormous efforts of Government and non-Government agencies with the help of world health organization (WHO) communicable diseases have been kept under control or some of them are eradicated; however, at the same time there is emergence of no ncommunicable diseases (NCD) like diabetes mellitus, hypertension, is chaemic heart disease, cancer and stroke which are partly due to increase of expectancy of life as well as sedentary life style faulty food habit and others. All the important NCDs are prevalent in the country of which stroke demands spinal attention due to increase morbidity and mortality. Stroke is one of the commonest neurological diseases that affect a significant number of the population in Bangladesh. Furthermore, there are other neurological diseases like head injury, brain tumor, epilepsy, meningitis, encephalitis and many more. Therefore a large number of patients admitted everyday into the hospital for treatment purposes. However, due to limited facilities of intensive care unit (ICU), hospital bed, and interventional neurology in the hospital these cause a great burden to the health sector of Bangladesh. In addition to that lack of advance technologies cause delayed diagnosis leading to influence the patients to go to abroad for better treatment. Therefore huge amount of foreign currencies are drained every year. Keeping all these things in mind the member of the society of Neurosciences have decided to establish National Institute of Neurosciences (NINS) in Bangladesh with the vision of making this Institute as the centre of excellence not only in this country but also for others. Ultimately the present NINS is the outcome of this effort. Currently this is the only referral tertiary care Neurology hospital in Bangladesh dealing with neurological as well as neurosurgical diseases. The current objective of NINS is to provide treatment to different neurological and neurosurgical cases in this country and to do the scientific research works as well as to collaborate with the other parallel institutes in abroad. It is a matter of pride that the institute has started functioning from September 2012 with OPD, IPD, emergency, ICU services as well as well equipped operation theater (OT) facilities. There are more than 15 departments related to neurological and neurosurgical diseases with more than 150 faculty members. Neurophysiology and interventional neurology are the two newly established departments which have been established first time ever in Bangladesh at public health sector. The NINS should be the centre of excellence in the country in near future where there should be the provision for one step services for the neurological cases. By this time the Institute has got its working life with the presence of 800 to 1000 patients in OPD everyday and 8 to 10 minor to major operation and the work in the Para clinical departments.