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Activation of KCNQ potassium channels by small chemical moleculars

Activation of KCNQ potassium channels by small chemical mole...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Zhaobing GAO~1,Min LI~(1,2) 1 State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences,555 Zu Chong Zhi Road,Zhangjiang Hi-Tech Park,Shanghai 201203,China 2 Department of Neuroscience,High Throughput Biology Center and Johns Hopkins Ion Channel Center,School of Medicine,Johns Hopkins University,Baltimore,Maryland 21205

KCNQ potassium channels play a critical role in controlling membrane *** a typical voltagegated ion channels(Kv),KCNQ channels undergo closed to open transitions by sensing transmembrane potential changes and mediate inhibitory potassium *** of KCNQ channel activity as results of genetic mutation is causal to a variety of human diseases including epilepsy,arrhythmia and ***,discovery of small compounds to activate voltage-gated ion channels is an important strategy for clinical intervention in human diseases caused by membrane hyperexcitability,including anxiety,epilepsy,arrhythmia and neuropathic *** the binding of these molecules induces a conformational change leading to the opening of these channels,there is also a considerable conceptual interest in understanding the molecular basis of these "gain of a function" *** molecule activators of cation channels are rare;however,several novel compounds have been identified for KCNQ potassium ***,we reported two new molecules which potentiate either cardical or neuronal KCNQ channels and identified molecular determinants for their activity,which provide exciting insights into activation of voltage-gated channels by small molecuars.

关键词： Activation of KCNQ potassium channels by small chemical moleculars

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Glutamate activated spinal astrocytes are involved in the thermal hyperalgesia

Glutamate activated spinal astrocytes are involved in the th...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Rui-Hong SHI,Xin ZHAO,Ce ZHANG~* Department of Physiology National Key Disciplines,Key Laboratory for Cellular Physiology of Ministry of Education,Shanxi Medical University,Taiyuan 030001,China

Objective Numerous evidence suggests that spinal astrocytes play an important role in chronic pain through release of neuroactive substances,such as interleukin and *** produces marked effects in initiation and transmission of nociceptive ***,there is a lack of direct evidence that how glutamate activate astrocytes and what's effects of activated astrocytes by glutamate on pain *** study therefore explored the direct effects of glutamate activation of spinal *** Primary culture of spinal astrocytes were administered with *** levels of protein and mRNA expression of IL-6,which reflect astrocyte activation, were determined by ELISA assay and real-time *** spinal astrocytes activated by glutamate were injected into the lumber enlargement of adult Wistar rats,and paw withdrawal latency(PWL) was *** Administration of glutamate(1 000 uM) activated astrocytes from 6 h after intrathecal injection and reached the maximal level at 24 h(the last time point we explored).Besides,glutamate(1 000 uM) enhanced the release of IL-6 by astrocytes. Intrathecal injection of cultured spinal astrocytes,which were stimulated by glutamate,induced a substantial decrease of PWL,indicating the development of thermal *** Our results suggest that activated astrocytes by glutamate is sufficient to produce thermal hyperalgesia in rats by releasing IL-6.

关键词： glutamate spinal astrocyte thermal hyperalgesia IL-6

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Amyloid precursor protein clusters at CNS nodes of Ranvier and causes an APPThr668 phosphorylation-dependent increase in Nav1.6 sodium channel currents

Amyloid precursor protein clusters at CNS nodes of Ranvier a...

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中国神经科学学会第九届全国学术会议暨第五届会员代表大会

作者： Shao LI Zhi-Cheng XIAO Quan-Hong MA Chao LIU Liang-Feng FAN Wu-Lin YANG Hong-Bin LI Toshitaka Futagawa Sashi Kesavapany Melitta Schachner Gavin S.Dawe Department of Physiology Dalian Medical University Dalian China Institute of Molecular Clinical medicine Kuming Medical College Institute of Neuroscience Soochow University Department of Clinical Research Singapore General Hospital Singapore Department of Biochemistry Yong Loo Lin School of Medicine National University of Singapore Singapore Zentrum fur Molekulare Neurobiologie University of Hamburg Hamburg Germany Department of Pharmacology and Department of Anatomy Yong Loo Lin School of Medicine National University of Singapore Singapore

APP, commonly associated with Alzheimer's disease, marks axonal *** physiological distribution and function along myelinated axons remain *** report that APP null and APP overexpressing transgenic (APPtg) mice show minor hypo-and hyper-myelination, *** axoglial interactions, APP aggregates at nodes of Ranvier (NORs) in the ***, coexpression of APP or its intracellular domains containing a VTPEER motif with Nav 1.6 sodium channels in Xenopus oocytes resulted in an increase in peak sodium currents, which was enhanced by APPT668E mutation and blocked by APPT668A mutation and inhibitors of CDK5 and *** cell surface expression of Navl.6 sodium channels in the white matter of spinal cord is decreased in APP, p35 and JNK3 null ***, APP, p35 and JNK3 deficiency significantly reduce spinal conduction ***, APP acts as a novel component at CNS NORs, modulating Navl.6 sodium channels in an APPThr668 phosphorylation-dependent manner.

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Microglial migration mediated by ATP-induced ATP release from lysosomes

Microglial migration mediated by ATP-induced ATP release fro...

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中国神经科学学会第九届全国学术会议暨第五届会员代表大会

作者： Ying DOU Hang-Jun WU Hui-Quan LI Song QIN Hui-Fang LOU Qing-Ming LUO Shu-Min DUAN Huazhong University of Science and Technology Wuhan 430074 China Department of Neurobiology Key Laboratory of Medical Neurobiology of the Ministry of Health of China Key Laboratory of Neurobiology of Zhejiang Province Zhejiang University School of Medicine Hangzhou 310058 China Huazhong University of Science and Technology Wuhan 430074 China Institute of Neuroscience and Key Laboratory of Neuroscience Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200031 China Department of Neurobiology Key Laboratory of Medical Neurobiology of the Ministry of Health of China Key Laboratory of Neurobiology of Zhejiang Province Zhejiang University School of Medicine Hangzhou 310058 China

Microglia are highly motile cells that act as the main form of active immune defense in the central nervous *** by factors released from damaged cells, microglia are recruited towards the damaged or infected site, where they are involved in degenerative and regenerative responses and phagocytotic clearance of cell *** release from damaged neural tissues has been suggested to mediate the rapid extension of microglial process towards the site of ***, the mechanisms of the long-range migration of microglia remain to be ***, we found that lysosomes in microglia contain abundant ATP and exhibit Ca2+-dependent exocytosis in response to various *** establishing an efficient in vitro chemotaxis assay, we demonstrated that endogenously-released ATP from microglia triggered by local microinjection of ATPγS is critical for the long-range chemotaxis of microglia, a response that was inhibited in microglia treated with an agent inducing lysosome osmodialysis or in cells deficient in Rab 27a, a small GTPase required for the trafficking and exocytosis of secretory *** results suggest that microglia respond to extracellular ATP by releasing ATP themselves through lysosomal exocytosis, thereby providing a positive-feedback mechanism to generate a long-range extracellular signal for attracting distant microglia to migrate towards and accumulate at the site of injury.

关键词： microglia migration ATP lysosome

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The role of proheparanase in synaptic plasticity of the hippocampus

The role of proheparanase in synaptic plasticity of the hipp...

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中国神经科学学会第九届全国学术会议暨第五届会员代表大会

作者： C.W.MA W.C.CHAM C.H.LAI D.K.Y.SHUM Y.S.CHAN Departments of Biochemistry and Physiology LKS Faculty of Medicine the University of Hong Kong Sassoon Road Hong Kong China Departments of Biochemistry LKS Faculty of Medicine the University of Hong Kong Sassoon Road Hong Kong China Departments of Physiology LKS Faculty of Medicine the University of Hong Kong Sassoon Road Hong Kong China

Perineuronal heparan sulfate (HS) moieties are implicated in the modulation of neurotransmission by controlling the functional properties of AMPA-type glutamate *** hypothesize that neuronal mechanisms modulate peri-synaptic HS level, thereby regulating synaptic strength and *** address this, basal synaptic strength and long-term changes in synaptic efficacy in the Schaffer collateral pathway of the rat hippocampus were assessed in relation to strategies that perturb peri-synaptic *** hippocampal slices, heparitinase treatment led to dose-dependent attenuation of long-term potentiation (LTP) in correlation with loss of perineuronal HS *** heparanase expression was found at the CA1 hippocampal neurons, we further tested if heparanase is the mammalian counterpart of heparitinase in the regulation of synaptic strength/*** asked therefore if neuronal heparanase is secreted as the pro-form or the active *** phorbol ester stimulation ofhippocampal neurons in culture, pericellular proheparanase accompanied by increase in enzymatically active heparanase in the cytoplasmic fraction was revealed by Western blot analysis of both the pericellular and cytoplasmic *** addition, treatment of the cultures with exogenous proheparanase triggered co-internalization of both cell-surface HS and AMPA *** use of calcium-imaging technique, proheparanase treatment was found to reduce glutamate-induced calcium influx of the hippocampal neurons in *** with these findings, treatment of hippocampal slices with exogenous proheparanase resulted in declines in both basal synaptic strength and *** together, our findings indicate neuronal secretion of proheparanase to peri-synaptic HS-sites as a novel mechanism that contributes to synaptic plasticity by regulating AMPA receptor level at the synapse.

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Indices of auditory response state characterized from the latency of local auditory evoked potentials

Indices of auditory response state characterized from the la...

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中国神经科学学会第九届全国学术会议暨第五届会员代表大会

作者： Fei-Xue LIANG Xiao-Jun ZHENG Qing-Kai DENG Zhong-Ju XIAO Department of Physiology Department of bioinformatics School of Basic Medical Sciences Southern Medical University Guangzhou 510515 China Department of Physiology School of Basic Medical Sciences Southern Medical University Guangzhou 510515 China Department of bioinformatics School of Basic Medical Sciences Southern Medical University Guangzhou 510515 China

The idea, auditory information might be encoded in the spike timing, rather than in neuronal firing rates, has been attracting increasing attention from the 90 s of last *** remains unclear, however, whether or not spike timing might encode the response state of auditory *** we investigated the latency characteristics of local auditory evoked potentials (LAEPs) in mice inferior colliculus during pentobarbital induced continuously change of response state of auditory *** intraperitoneal infusion of sodium pentobarbital, LAEPs evoked by different stimulus intensities were recorded as a dataset every 10 minutes (defined as a recording session).Then the latency from the beginning of sound delivery to the first negative peak (N 1) of each LAEP on all the recording sessions during anesthesia was extracted and plotted as a function of stimulus *** further analysis the data, we employed a double coordinate axis fitting shift algorithm (DCAFSA) basing on Pieron's empirical law to calculate the latency shift of each latency-intensity function, which were plotted as a function of recording *** result showed that the latency shift prolonged to a plateau and then shortened smoothly with recording session after the pentobarbital ***, similar phenomenon was more clearly observed across populations of recording sites and *** abdominal administration, the absorption and metabolism of anesthetics would result in a reversible time-effect relationship, which will change the response state of auditory system in ***, the latency shift of LAEPs is a potential index to quantitatively encode the auditory response state.

关键词： response state of auditory system local auditory evoked potentials latency shift

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Transient cerebral ischemia induces long-term axonopathy:Its importance for the risk of Alzheimer's disease

Transient cerebral ischemia induces long-term axonopathy:Its...

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中国神经科学学会第九届全国学术会议暨第五届会员代表大会

作者： Qin-An ZHANG Teng GAO Yi LUO Xi-Juan CHEN Ge GAO Xiao-Qun GAO Yi-Wu ZHOU Paul J.LUCASSEN Jia-Pei DAI Department of Anatomy Brain Paralysis Research Center Medical College of Zhengzhou University Zhengzhou 450052 China Wuhan Institute for Neuroscience and Neuroengineering South-Central University for Nationalities Wuhan 430074 China Department of Forensic Medicine Tongji Medical College of Huazhong University of Science & Technology Wuhan 430030 China Swammerdam Institute for Life Sciences Center for Neuroscience University of Amsterdam Amsterdam the Netherlands

Objective Cerebral ischemia may contribute to the pathogenesis of Alzheimer's disease (AD), however, the neuropathological relationship between these 2 disorders is largely *** investigated axonal changes after transient cerebral ischemia/reperfusion and their relationship to the expression of Aβ42 and hyperphosphorylated Tau, which has been considered as a key neuropathological process of *** Adult Wistar rats were subjected to either sham operation or middle cerebral artery occlusion (MCAO).At the desired time after the onset of reperfusion (6 h, 24 h, 1 w, 2 w, 3 w and 4 w), animals were carried out for in vivo tracing and sacrificed for tracer detection, immunochemistry and morphological analysis of axons, and immunoblotting test for hyperphosphorylated Tau was also *** Axonal changes, consisting of swollen axons and varicosities, were found 6 h after ischemia/reperfusion in ischemic regions, such as the sensory and motor cortex and striatum, as well as the perilesional cortex and hippocampus, and were observed for up to 4 *** did not observe Aβ plaques or overexpression of Aβ42 in the ischemic brain areas; nevertheless, site-specific hyperphosphorylated Tau could be detected in the ischemic *** Transient cerebral ischemia/reperfusion induces long-term axonal changes (axonopathy), which may be an important mechanism contributing to the development of AD after stroke.

关键词： cerebral ischemia axonopathy stroke Alzheimer' s disease

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Reference values for amplitude-integrated electroencephalogram in infants from preterm to 3.5 months of age

Reference values for amplitude-integrated electroencephalogr...

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中国神经科学学会第九届全国学术会议暨第五届会员代表大会

作者： Dan-Dan ZHANG Yun-Feng LIU Da-Tian YE Yue-Jia LUO Department of Biomedical Engineering Tsinghua University Beijing 100084 China Department of Pediatrics Peking University First Hospital Beijing 100034 China Department of Biomedical Engineering Tsinghua University Beijing 100084 China State Key Laboratory of Cognitive Neuroscience and Learning Beijing Normal University Beijing 100875 China State Key Laboratory of Cognitive Neuroscience and Learning Beijing Normal University Beijing 100875 China

Objective Amplitude-integrated electroencephalogram (aEEG) is a valuable tool for the continuous evaluation of functional brain maturation in *** amplitudes of the upper and lower margins of aEEG are postulated to change with maturation and correlate with postmenstrual age (PMA).This study aimed to establish reliable reference values of aEEG amplitudes, providing quantitative guidelines for assessing aEEG maturation in neonates and young *** Normal infants (n =274) with PMAs that ranged from 30 to 55 weeks were divided into ten groups according to their *** 5-min segments were selected from each aEEG to calculate the upper/lower margin and bandwidths of the tracing *** Interobserver agreement was achieved with an overall correlation of *** upper and lower margins of aEEG in both active and quiet sleep clearly rose in infants beyond the neonatal *** bandwidth defined as the graphic distance decreased almost monotonically throughout the PMA range from 30 to 55 *** lower margin of aEEG was positively correlated with PMA, with a larger rank correlation coefficient during quiet sleep (r =0.89) than during active sleep (r =0.49).Conclusion Reference values of aEEG amplitudes were obtained in infants with a wide range of PMA and constitute a basis for the quantitative assessment of aEEG maturation in neonates and young *** normative amplitudes of aEEG margins, especially of the lower margin in quiet sleep, are recommended as reference data for the identification of potentially abnormal aEEG.

关键词： amplitude integrated EEG infant reference values upper and lower margins

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Role of different subunit-containing NMDA-receptors in retinal spreading depression

Role of different subunit-containing NMDA-receptors in retin...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Paul L Chazot Sura Ali Stevens F Duckett Tihomir P Obrenovitch Department of Biological Sciences University of DurhamDurham DHl 3LEUK School of Pharmacy and Biomedical Sciences University of Central LancashirePreston PR12HEUK School of Pharmacy University of BradfordBradford BD7 1DPUK

Spreading depression(SD) is a temporary disruption of local ionic homeostasis that propagates slowly across the *** depolarisation associated with SD occurs in different types of stroke and may contribute to the initiation of migraine *** receptor(NMDAR) antagonists are known to be the most effective drμgs to suppress *** far,NMDAR antagonist are still perceived as unlikely candidate as anti-SD drμg for migraine aura treatment because of their unacceptable side effects,but the NMDAR antagonist,memantine is now used chronically in elderly for Alzheimer's and epilepsy patients and some subtype selective receptor antagonists may well be effective with reduced side *** an efficient in vitro chick retinal SD model with imaging for NMDAR pharmacology, we have determined whether NMDAR antagonists,with different type NR2 subunit selectivity,can suppress spreading depolarization associated with SD in the chicken retina *** results sμggested NR2A plays a key role in mediating SD,indicating potential therapeutic benefit for NR2A-preferring antagonist to treat SD-related neurological diseases,*** with alleviated side effect.

关键词： Role of different subunit-containing NMDA-receptors in retinal spreading depression

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The neurovascular imaging in cerebral ischemia by laser speckle contrast analysis

The neurovascular imaging in cerebral ischemia by laser spec...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Shan-Bao TONG~*,Peng MIAO,Min-Heng LI,Hong-Yang LU,Qi LIU,Yao LI School of Biomedical Engineering,Shanghai Jiao Tong University,Shanghai 2000240,China

Objective Laser speckle contrast analysis has been used in imaging the cerebral vasculature and cerebral blood flow(CBF).However,in practice,the estimation of the CBF may be biased by the ambient background field, dark current and other anomalies in the circuits of CCD camera,non-uniform distributed laser illumination,cortical curvature,breathing/heart beating of the subjects,and the nonstationary change of CBF under functional stimulation, and the motion artifacts if applied to the behavioring *** In order to obtain a stable and high spatiotemporal resolution CBF imaging in the study of the ischemic brain injury,we developed several techniques to improve the current techniques of laser speckle contrast analysis,including(1) enhanced laser speckle contrast analysis (eLASCA);(2) model Based LSI reconstruction;(3) registered laser speckle contrast analysis(rLASCA);(4) Random process estimator for laser speckle *** finally we integrate these techniques and designed a miniature headstage imaging system which can be used to obtain the CBF imaging when the animal(***) is moving freely. Results By using the above techniques,high resolution CBF information can be obtained in real time for either anesthetized or freely moving *** We developed high-resolution optical imaging technique for CBF monitoring,which can be used for real time monitoring both structural and functional neurovascular changing in ischemic brain injury.

关键词： neurovascular imaging cerebral blood flow laser speckle imaging laser speckle contrast analysis

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