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Possible protective role of Ceylon tea on Spinocerebellar Ataxias- A pilot study

Possible protective role of Ceylon tea on Spinocerebellar At...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Gonawala BL Gunasekara H Sirisena D Wijekoon DNB Amaratunga D Faruq M Dalal A De Silva KRD Genetic Diagnostic & Research Laboratory Faculty of Medical SciencesUniversity of Sri Jayewardenepura

Introduction- Spinocerebellar ataxias(SCAs) are a group of heterogeneous neurodegenerative disorders. Compromised oxidative stress defense capacity and mitochondrial dysfunction due to cytoplasmic and nuclear aggregate formation of mutant proteins have emerged as contributing factors to the pathogenesis of polyQ diseases. Objective- To assess clinical and genetic features and to investigate the effect of black tea against disease progression in SCA cohorts in Sri Lanka. Methods- Clinically diagnosed SCA patients [n=20, age range 30-67, Male- 11(55%), Female- 9(45%)] from neurology clinics at two tertiary hospitals were studied. Sociodemographic factors, clinical data, family history and Consumption of tea were obtained using a standard questionnaire. Patients were subjected to genotyping for SCA1, SCA2 and SCA3. Results–SCA patients age of onset 21-64yrs(mean= 39±13.7) Familial inheritance n=13(65%);paternal inheritance n=12(92%). Genotyping distinguished SCA subtypes;SCA1(n=6, 30%), SCA2(n=1, 5%) and SCA3(n=4, 20%) while remaining were negetive for studied subtypes. Black tea consumption & Scale for the Assessment and Rating of Ataxia(SARA) score range was between 5.5-24(mean = 14.9 ± 5.7). Patients with tea consumption 3 cups/day n =5, mean SARA score = 13.2;2 cups/day n =9, mean SARA score = 13.9;1cups/day n =6, mean SARA score = 17.7 Conclusion- Regular consumption of black tea indicates a trend towards lowering the risk of motor impairment in SCA. This study may suggest justification in exploring regional natural product based nutraceuticals to enhance quality of life through preventing aggregation of mutant protein.

关键词： spinocerebellar ataxias tea genetics Sri Lanka

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Entinostat-attenuated DNA repair protein MGMT plays a crucially synergistic role in temozolomide-injured glioblastomas cells

Entinostat-attenuated DNA repair protein MGMT plays a crucia...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Zong-yang Li Lei Chen Ce Zhang Yi-sha Wang Wei-ping Li Department of Neurosurgery Shenzhen 2nd People's Hospital Shenzhen University 1st Affiliated Hospital

Malignant glioblastomas(GBM) are the most common and most aggressive type of primary adult brain tumor, accounting for approximately 15% of all intracranial tumors. Median survival after treatment is around 12 months, however, advances in therapy these tumors remain associated with poor prognosis. Conventional treatments include surgery, radiotherapy, and chemotherapy, which is mainly based on the alkylating agent Temozolomide(TMZ), however, TMZ-induced multidrug resistance(MDR)after long-term treatments, contributing to a poor prognosis in GBM treatment. As analkylating chemotherapeutic agent, TMZ would cause DNA damage by the transfer of alkyl groups at several sites within DNA, but certain studies have revealed that TMZ could induced the activation of O6-methylguanine-DNA-methyl-transferase(MGMT) gene which promoted the encoding of the suicide DNA repair protein that removed alkyl groups from O6-guanine, thus to counteract the therapeutic effect of TMZ and correlate with deteriorated survival in glioma patients. In the meantime, tumors often show hyperactive PI3-kinase/mT OR pathway, which facilitated them to re-synthesis proteins quickly, therefore, it has been hypothesized that inhibition of translation via the m TOR signaling pathway could generate atumor-specific reduction in MGMT protein and increase TMZ sensitivity. Histone deacetylase(HDAC) inhibitors are becoming a novel and promising class of antineoplastic agents that have been used for cancer therapy in the ***, abundant studies just focused on the cytotoxicity induced by the single treatments of HDAC inhibitors, the combinations of drug therapy were relatively paid less attention. The purpose of this study was to examine the efficiency and mechanisms of Entinostat(a HDAC1 inhibitor) in synergistic concomitant and adjuvant withalkylating agent(TMZ) in GBM therapy in vitro model, and investigated whether the post-translational modification of HDAC inhibitors to the protein synthesis and

关键词： Entinostat MGMT temozolomide glioblastomas HDAC

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GIRK channel hyperpolarized the membrane potential and inhibited the epileptiform activities in the cultured hippocampal neurons

GIRK channel hyperpolarized the membrane potential and inhib...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Yi-An HUANG Li WAN Liang REN Yun WANG Institutes of Brain Sciences and State Key Laboratory for Medical Neurobiology Fudan University

Objective G-protein gated inwardly rectifying potassium channel（GIRK） is a kind of ligand-gated potassium channel. In central nervous system, most of the potassium channels are voltage-gated. GIRK channel, and calcium-activated potassium channel（Kca） are two special kinds of potassium channel groups, which may open in the presence of ligand, although they are still under the modulation of different voltages. Most of the previous works concentrated on the physiological properties of GIRK channel. However, the role and mechanism of GIRK channel in the disease pathology are still not clear. Our aim is to observe the dynamics of GIRK channel in the epileptic processes. Methods Most of our works were based on the electrophysiological technology, by using patch clamp recording. We used two ways to record GIRK current, one by the drug puff of baclofen（200μM）, a kind of GIRK channel ligand, also the GABAB receptor agonist, another by the holding potential ladder（-160 m V 80 m V, 20 m V step）, to measure the GIRK current in different membrane potentials. Convulsant cyclothiazide（5μM） was used to induce epileptiform activities in the cultured hippocampal neurons. Action potentials and burst activities were the major parameters to measure the strength of epileptiform activities. Results We found that GIRK channel was an important potassium channel, which produced about half of the total inwardly rectifying potassium currents（about 42%4%）. GIRK channel plays some important roles in the normal physiological activities of central nervous system. One of them is the membrane potential maintenance. Our experimental results demonstrate that, GIRK current decreased in the epileptic model induced by convulsant cyclothiazide, both in the acute period（20min, 2h） and long-time period（48h）. On the Contrary, in the condition of GIRK inhibition by antagonist tertiapin Q（100n M）, the probability of neurons showing epileptiform burst activity significant increased（from 23% to 54%）. Then we tri

关键词： G-protein gated inwardly rectifying potassium channel epilepsy cultured hippocampal neuron patch clamp recording

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Effects of green tea polyphenols on motor,learning and memory functions of model mice of Parkinson's disease

Effects of green tea polyphenols on motor,learning and memor...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Yu-Chen Fu Meng-Meng Zheng Jun Wang Qing-Qing Wang Ting-Ting Zhou Meng-Ya Wang Cell Electrophysiology Laboratory Wannan Medical College Rising-Star Group Wannan Medical College

Objective To explore effects of green tea polyphenols(GTPs) on motor, learning and memory functions of model mice of Parkinson's disease(PD) and possibly to offer the experimental data of GTPs application in clinical PD patients. Methods Fifteen male C57 BL mice were randomly divided into saline, low dosage(100 mg/kg) and high dosage(625 mg/kg) group of GTPs. After testing of Morris water maze, Rotor-rod system and pole-climbing, mice in 3 groups were administered with MPTP(30mg/kg, i.p., q.d.) for 7 days to prepare animal model. Then the 3 types of testing were performed to evaluate the PD mice, Thereafter, mice in low and high dosage groups received GTPs treatment(i.p., q.d.) for 14 days, while saline group mice were given equivalent amount of saline. The 3 types of testing were repeated on the 7th and 14 th day of GTPs treatment. Results MPTP application lengthened the escape latency of Morris water maze and the time of pole-climbing, and shortened the lasting time of rotor-rod system climbing(n=15, P<0.05). Comparing to the saline group, GTPs not only shortened the escape latency of Morris water maze and the time of pole-climbing, but also lengthened the lasting time of rotor-rod system climbing(P<0.05). Conclusions MPTP impairs the motor, learning and memory function of C57 BL mice, but GTPs presents relieving effects on PD mice and may be a candidate drug to treat PD patients.

关键词： Parkinson's disease green tea polyphenols learning and memory dyskinesia

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The enhancement of the transfer efficiency of LFPs theta network during a working memory task in rat by rTMS

The enhancement of the transfer efficiency of LFPs theta net...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Meng-Meng Dou Wen-Wen Bai Xin Tian Laboratory of Neurobiology in Medicine School of Biomedical EngineeringTianjin Medical University

Objective Working memory(WM) is necessary in higher cognition. The concept of brain network plays an important role in neuroscience as a useful tool to understand the organized behavior of brain. Previous studies suggested that noninvasively repetitive transcranial magnetic stimulation(rT MS) induced potentiation effect on learning and memory ability of rats. The aim is to analyze the local field potentials(LFPs) functional connectivity and transfer efficiency of brain network, to achieve a better understanding of the effect of rT MS during a working memory task. Methods Male SD rats were divided randomly into two groups, namely Con group and r TMS group. Rats in r TMS group were treated by one low-frequency(1 Hz) r TMS session(400 stimuli, 0.4Tesla) daily for 14 consecutive days. Multi-channel LFPs were obtained from rat prefrontal cortex with implanted microelectrode arrays while the rats performed a Y-maze working memory task. The short-time Fourier transform was utilized to analyze the power changes in LFPs and theta(4-12 Hz) bands were extracted via band filtering. Then the Directed transfer function(DTF) method was applied to calculate the functional connections among LFPs and the brain network was structured. Then the transfer efficiency of brain network(E) in two groups was calculated. Results The time-frequency results show that the maximum of power appears in theta band before the choice point. The E-curve also peaked before thechoice point, and the transfer efficiency values are significant differences between r TMS(0.046±0.0043) and Con(0.028±0.0038)(n=10, P<0.01). Conclusion The main frequency component of the working memory is theta band. And r TMS can enhance the transfer efficiency of brain network during a working memory task.

关键词： working memory rTMS local field potentials(LFPs) DTF network transfer efficiency

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Dynamic and diverse modulation of connexin phosphorylation in mirror image pain

Dynamic and diverse modulation of connexin phosphorylation i...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Qing-Hu Yang Xiang-Xiang Chen Lei Xi Hong-Ni Zhu Xiao-Xia Zhao Jia-Jing He Cheng-Hui Cao Jia Li Xia Liu Zhi-Hong Sun Zhan-Tao Bai College of Life Sciences Yanan University Shaanxi Engineering & Technological Research Center for Conversation & Utilization of Regional Biological Resources Shaanxi Provincial Key Lab of Red Dates

Gap junctions(GJ) play an important role in intercellular communication between adjacent cells. The protein expression, membrane cluster, subtype couple, pore selectivity and gating of GJs might be regulated by phosphorylation of connexins. Combining with behavioral observation, quantitative real-time PCR, immunoblotting, immunofluorescence, live cell imaging and other techniques, we found that GJ whole channels or hemichannels between glia-glia, glia-neurons showed in diverse cellular specific subtypes, distribution, phosphorylation, and thus modulated induction, development and maintenance of mirror image pain. Moreover, the temporal-spatial expression of connexins changed distinctly in rat spinal cord and dorsal root ganglion(DRG), and was asymmetrical at both sides to noxious stimuli. Furthermore, diverse phosphorylational sites of connexins such as Cx 43, by different protein kinases including PKA, PKC, MAPK and src, were relative to gating, transcription, translation and post-translational trafficking of GJs, by which to meet synaptic transmission in spinal and DRG control of mirror image pain. These results indicate that differential temporal-spatial expression and dynamic phosphorylation of connexins, especially Cx 43, if any more, is one of indispensable peripheral and central modulation to induction and spreading of mirror image pain.

关键词： Gap junctions Connexins Mirror image pain Phosphorylation

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MSX3 switches microglia polarization and protects from inflammation induced demyelination

MSX3 switches microglia polarization and protects from infla...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Zhongwang Yu Dingya Sun Jifeng Feng Weixing Tan Xue Fang Ming Zhao Xiaolin Zhao Yingyan Pu Aijun Huang Zhenghua Xiang Li Cao Cheng He Institute of Neuroscience and Key Laboratory of Molecular Neurobiology of the Ministry of Education Neuroscience Research Center of Changzheng HospitalSecond Military Medical University

The major challenge for progressive multiple sclerosis therapy is the promotion of remyelination from inflammation-induced demyelination. A switch from an M1- to an M2-dominant polarization of microglia is critical in these repair processes. In this study, we identified the homeobox gene msh-like homeobox-3(MSX3) as a new pivotal regulator for microglial polarization. MSX3 was induced during microglia M2 polarization and repressed in M1 cells. The expression of MSX3 in microglia was dynamically regulated during experimental autoimmune encephalomyelitis(EAE), which is an animal model of multiple sclerosis. The over-expression of MSX3 in microglia promoted M2 but impeded M1 polarization. Interrupting MSX3 expression in microglia accelerated inflammation-induced demyelination and neurodegeneration. The condition medium from MSX3-transduced microglia promoted oligodendrocyte progenitor survival, differentiation and neurite outgrowth. The adoptive transfer of MSX3-transduced microglia suppressed EAE and facilitated remyelination within the murine CNS in EAE and LPA model. Mechanically, Ch IP assays also indicated that MSX3 directly regulated three key genes associated with microglia M2 polarization, including PPARγ, STAT6 and JAK3. Importantly, we found that over-expression of MSX3 in human-derived microglia represents the M2 phenotype and ameliorated EAE following intra-ventricular injection. Our findings suggest a new homeobox protein-dependent mechanism for driving microglia M2 polarization and identify MSX3 as an attractive therapeutic approach for preventing inflammation-induced demyelination and promoting remyelination.

关键词： multiple sclerosis EAE microglia polarization MSX3

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Potential of stem cells in therapy for inner ear

Potential of stem cells in therapy for inner ear

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Xiang-xin Lou Department of Bioengineering College of ChemistryChemical Engineering and BiotechnologyDonghua University

In vertebrates, perception of sound, motion, and balance is mediated through sensorineural hair cells and spiral ganglion neurons located within the inner ear. Hair cells are only generated during a short period of embryonic development in mammals. As a result, loss of hair cells as a consequence of injury, disease, or genetic mutation, always leads to permanent sensory deficits. At present, cochlear implantation is the only option for profound hearing loss. However, outcomes are still variable and even the best implant cannot provide the acuity of a biological ear. The recent emergence of stem cell technology has the potential to open new approaches for hair cell regeneration. Previous reports show that early postnatal cochlea harbors stem/progenitor-like cells nominated otospheres which have a limited regenerative/repair capacity, while these cell populations are progressively lost during the postnatal development. Induced pluripotent stem cells(iP SCs) directly reprogrammed from non-embryonic cells have captured great attentions in the scientific community. In the present study, we determine whether Yamanaka's factors can induce the reprogramming of inner ear cells into i PS cells. We introduced defined factors Oct3/4, Sox2 and Klf4 into otospheres derived from postnatal day-1(P1) mouse SE, and analyze characteristics alterations in cochlear cells. After transduction, otospheres generated colonies exhibiting a normal karyotype and morphology similar to that of mouse embryonicstem cells(ESCs). Moreover, these cochlear iP SCs also expressed ESC-like markers. Importantly, the cochlear iP SCs show pluripotency in vitro and in vivo, as evidenced by differentiation into three germ layers by embryoid body formation, as well as high efficient formation of teratomas containing three germ layers in immunodeficient mice. Thus, pluripotent cochlear iP SCs can be generated from cochlear cells by using three Yamanaka's transcription factors. These attempts represent the first

关键词： induced pluripotent stem cells reprogramming inner ear retrovirus

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Downregulation of G protein coupled receptor kinase 6 mediates chronic visceral hypersensitivity through activation of adrenergic signaling pathway in rats with neonatal colonic inflammation

Downregulation of G protein coupled receptor kinase 6 mediat...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Zhou Yuan Hu Shu-Fen Xu Guang-Yin Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases Institute of NeuroscienceSoochow University Department of Anesthesiology Affiliated Hospital of Nantong University

Objective The pathogenesis of irritable bowel syndrome(IBS)remains poorly understood and treatment options are very limited. The aim of present study was to explore the roles of G protein-coupled receptor kinase 6(GRK6) and β2-adrenergic receptor(β2-AR) signaling pathways in chronic visceral pain in a rat model of IBS induced by neonatal colonic inflammation(NCI). Methods Abdominal withdrawal reflex(AWR) scores to grade colorectal distention in adult male rats were recorded as a measure of visceral hypersensitivity. Western blot analysis and immunofluorescence were performed to examine protein expression. Over-expression GRK6 via lentivirus intrathecal injection was used to neutralize the effect of GRK6 in NCI model. Co-immunoprecipition assay was employed to identify the interaction between GRK6 and β2-AR. Results NCI significantly increased AWR scores and down-regulated expression of GRK6 in colonic dorsal root ganglion(DRGs) when compared with age-matched controls. NCI produced a significant elevation of norepinephrine concentration and β2-AR expression in DRGs. Administration of β2-AR antagonist butoxamine reversed NCI-induced visceral hypersensitivity. Importantly, over-expression GRK6 by intrathecal lentivirus injection markedly attenuated NCI-induced visceral hypersensitivity and reversed the up-regulation of β2-AR expression. Furthermore, co-immunoprecipitation showed the interaction between GRK6 and β2-AR. Conclusion Our data suggests that decreased expression of GRK6 mediates NCI-induced chronic visceral pain through activation of β2-AR signaling pathway. This finding may identify a potential target for treating chronic visceral pain caused by IBS.

关键词： Irritable bowel syndrome visceral hypersensitivity neonatal colonic inflammation G protein coupled receptor kinase 6 β2-adrenergic receptors dorsal root ganglion

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Neuronal representation of computation of saccadic errors in macaque lateral intraparietal cortex(LIP)

Neuronal representation of computation of saccadic errors in...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Yang Zhou Yining Liu Si Wu Haidong Lu Mingsha Zhang State Key Laboratory of Cognitive Neuroscience and Learning Beijing Normal University Institute of Neuroscience Shanghai Institutes for Biological SciencesChinese Academy of Sciences University of Chinese Academy of Sciences The First Affiliated Hospital of Zhengzhou University

Objective Two types of signals in the brain code the position of motor effectors, i.e., endogenous signals(e.g., corollary discharge) and exogenous signals(e.g., proprioception). During self-oriented movements, the internally generated signals predict the required future position of motor effectors, whereas the externally generated signals inform their real positions. It has been argued that the comparison/integration of these two types of signals play a crucial role in motor control, motor learning, self-recognition and spatial perception. However, despite knowing that the frontoparietal lobes are involved in such signal integration, the underlying neural mechanisms are largely unknown. Methods: To address this question, we studied the signal integration of eye position during saccadic eye movements. We recorded single neuron's activity from the macaque lateral intraparietal cortex(LIP) while the animals were performing oculomotor tasks. LIP is a node that is used to link visual and oculomotor systems, which plays crucial roles in visual attention, saccadic planning and related cognitive processing. Results: Here, we report the co-existence of the predictive and real eye position signals in LIP: neurons with pre- and postsaccadic response predict the required future eye position;neurons with late postsaccadic response represent the extraocular proprioceptive signals. Moreover, the persistent pre- and postsaccadic response neurons behave like a "subtraction operator" to measure the discrepancy between the two types of signals. Their post-operated activity level is highly correlated with the animal's behavioral performance, e.g., the higher the post-operated activity(reflecting the greater incongruence between internal and external signals), the larger the saccadic error(distance between saccade end points and saccadic target) and the higher the probability of making corrective saccades. Conclusion: The correlation between neural activity and the animals' behavioral

关键词： Motor error Internal signal External signal Signal comparison Lateral Intraparietal Area(LIP)

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