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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 PDE4 and its PDE4D isoenzymes in emotional-related behaviors

Role of PDE4 and its PDE4D isoenzymes in emotional-related b...

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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： Marco Conti Steven P.Wilson James M.O'Donnell Department of Obstetrics and Gynecology University of California Department of Pharmacology Physiologyand NeuroscienceUniversity of South Carolina School of Medicine

＜正＞Objective Inhibition of phosphodiesterase-4（PDE4） increases phosphorylation of the cAMP response element binding protein（pCREB） and hippocampal neurogenesis,and produces antidepressant-like and cognitiveenhancing *** study is to establish causal links among these actions and explore the splice variants of PDE4 responsible for emotional-related *** Using tests sensitive to antidepressant and anxiolytic drugs,the emotional-related behavioral effects were *** hippocampal neurogenesis and pCREB expression were measured by fluorescence ***-form PDE4Ds were silenced by the bilateral microinfusion of lentiviral vector containing PDE4D microRNAs（4DmiR） into the prefrontal cortex（PFC）.Cognitive behaviors were measured by novel object recognition test（NOR） and Morris water maze test（MWM）.The emetic potential was evaluated by the assessment of the anaesthetic reversal *** levels of cAMP and proteins were determined by ELISA and immunoblotting analyses,***（1） Chronic administration of rolipram（0.31-1.25 mg/ kg,16-23 days） produced antidepressant- and anxiolytic-like effects in *** also increased cAMP and pCREB levels in the hippocampus and prefrontal cortex,but increased Sox2,a marker for mitotic progenitor cells,only in the hippocampus.（2） Chronic rolipram treatment also increased hippocampal neurogenesis;Methylazoxymethanol （MAM）,a toxin to proliferating cells,reversed rolipram-induced increases in BrdU-positive cells and pCREB in the hippocampus and partially blocked its behavioral effects.（3） Rolipram and MAM didn’t alter the percentage of newborn neurons or pCREB in BrdU-positive cells.（4） As rolipram-treated wild-type mice,PDE4D-deficient mice also displayed increased hippocampal neurogenesis and pCREB,which were not altered by rolipram.（5） Two weeks after the bilateral PFC microinfusion,4DmiR down-regulated PDE4D4/5 splice variants,but not PDE4A,PDE4B.（6） Rolipram and/or 4DmiR treatments

关键词： phosphodiesterase-4 PDE4D RNA interference neurogenesis cAMP CREB hippocampus prefrontal cortex

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Glycine exerts dual roles in ischaemic injury through distinct mechanisms

Glycine exerts dual roles in ischaemic injury through distin...

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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： Wen YAO~(1,2,#).Fang JI~(1,2,#),Zheng CHEN~(1,2),Si-Qiang REN~(1,2),Xiao-Yan ZHANG~(1,2),Su-Yi LIU~(1,2),Wei LU~(1,2,3,4,*) 1 Department of Neurobiology,Nanjing 210029,China 2Key Laboratory for Neurodegenerative Disease of Jiangsu Province,Nanjing 210029,China 3Lab of Reproductive Medicine,Nanjing 210029,China 4Key Laboratory for Human Functional Genomics of Jiangsu Province,Nanjing 210029,China

Ischemia elicits rapid release of various amino acids including glycine,which is the co-agonist of NMDA receptor(NMDAR)and one of main inhibitory neurotransmitters in central nervous *** accumulating studies has aimed to illustrate the exact effect of glycine in development of post-ischaemic brain injury,the results remain quite *** controversies mainly involve whether glycine exerts deleterious or neuroprotective effect in ischemia and by which mechanism glycine displays its ***,we report that glycine exerts dosedependent bidirectional effects on ischaemic injury in both in vitro and in vivo stroke *** in vitro stroke model induced by oxygen and glucose deprivation(OGD),glycine at relatively low level,achieved either by exogenous application or by elevating endogenous glycine accumulation with an antagonist of the glycine transporter,potentiated pathological post-ischaemic long-term potentiation(i-LTP).By contrast,glycine at high level totally abolished i-LTP. Similar observations,manifested by bifurcated effects of glycine in infarct volume,were also observed in in vivo stroke model produced by middle cerebral artery occlusion(MCAO).These data suggest that the level of glycine is a critical factor in determining the direction of its role in regulating ischaemic *** evidence demonstrated that the deleterious effect exerted by low level glycine was mediated by its modulation on NMDAR co-agonist site (site B),whereas neuroprotective effect of high level glycine was mediated by glycine receptor(site A)activation and subsequent differential regulation of NMDAR NR2 subunit components in in vitro and in vivo stroke ***, our present results provide a molecular basis for the dual roles of glycine in facilitation or correction of ischaemic injury through distinct mechanisms and suggest that glycine receptor could be a potential target for clinical treatment of stroke.

关键词： glycine glycine receptor NMDA receptor ischemia hippocampus

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Tri-lithium pyrroloquinoline quinine ameliorates cognitive impairment and extenuates cerebral pathological lesions in amyloid precursor protein/presenilin-1 transgenic mice

Tri-lithium pyrroloquinoline quinine ameliorates cognitive i...

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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： Lei ZHAO~1,Neng GONG~2,Zhe YU~2,Qi FANG~2,Tian-Le XU~(2,*),Chun-Jiu ZHONG~(1,*) 1 Department of Neurology,Zhongshan Hospital,Fudan Univeristy,Shanghai 200032,China 2 Institute of Neuroscience,State Key Laboratory of Neuroscience,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences,Shanghai 200031,China

Alzheimer's disease（AD） is the most common age-related neurodegenerative disorder and cause of dementia in the elderly,characterized by global cognitive impairment and the presence of extracellular beta-amyloid （Aβ） deposition（senile plaques） and intracellular hyperphosphorylated tau protein（neurofibrillary tangles）.Currently, the dominant theory to explain pathogenesis of AD is the "Amyloid Cascade Hypothesis" first proposed in 1992. However,almost all previous clinical trials targeting Aβhave received negative *** disappointing fact triggers us to reconsider this hypothesis and to explore more effective treatment *** drastic disturbance of glucose metabolism in the brain is one of the striking features of AD.A significant reduction in cerebral glucose consumption precedes overt clinical symptoms or brain atrophy,even for *** studies have demonstrated multiple defects in glucose and energy metabolism in AD ***,the decreased glucose and energy metabolism induces various pathogeneses similar to AD such as oxidative stress,activated glucose synthase kinase-3（GSK-3） signal pathway,and excitatory and inhibitory signaling dysfunction,and so ***,the drug or therapy only targeting to a single mechanism is difficult to modify the *** is essential to design new treatment strategy that can rectify the disturbed cellular energy metabolism and stop the multiple pathogenic cascades ***,a GSK- 3 inhibitor,has been demonstrated the beneficial effect on *** quinone,a new B vitamin,has been demonstrated neuroprotective action through the mechanisms of powerful anti-oxidation and improving mitochondria *** independently synthesized tri-lithium pyrroloquinoline quinone（LiPQQ）.We found that LiPQQ exhibited a very low acute toxicity（LiPQQ ID50 2.50 g/kg weight vs LiC1 ID50 0.53 g/kg weight） by evaluating acute toxicity with *** use the amyloid precursor protein/presenilin-1（APP/PSl）

关键词： lithium pyrroloquinoline quinine Alzheimer's disease

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Functional recovery in acute traumatic spinal cord injury after transplantation of human umbilical cord mesenchymal stem cells

Functional recovery in acute traumatic spinal cord injury af...

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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： Sheng-Li HU,Hai-Shui LUO,Jiang-Tao LI,Yong-Zhi XIA,Lan LI,Li-Jun ZHANG,Hui MENG,Gao-Yu CUI,Zhi CHEN, Nan WU,Jiang-Kai LIN,Gang ZHU,Hua FENG Department of Neurosurgery,Southwest Hospital,the Third Military Medical University,Chongqing 400038,China

Objective Spinal cord injury results in loss of neurons,degen eration of axons,formation of glial scar,and severe functional immunofluorescence *** umbilical cord mesenchymal stem cells can be induced to form neural cells in ***,these cells have a significantly enhanced potential therapeutic role for treating spinal cord *** and Setting Rats were randomly divided into three groups:sham operation group,control group, and human umbilical cord mesenchymal stem cell *** groups were subjected to tures around the lesion site by weight drop device except for sham *** Thirty-six female Sprague-Dawley *** The control group received Dulbecco's modified media/nutrient mixture F-12 injections,whereas the human umbilical cord mesenchymal stem cell group undertook human umbilical cord mesenchymal stem cells transplantation at the dorsal spinal cord 2 mm rostrally and 2 mm caudally to the injury site at 24 hrs after spinal cord *** Rats from each group were examined for neurologic function and contents of brain-derived neurotrophic factor. Survival,migration,and differentiation of glial scar were also explored by using immunohistochemistry and *** results Recovery of hindlimb locomotor function was significantly enhanced in the human umbilical cord mesenchymal stem cells grafted animals at 5 wks after *** recovery was accompanied by increased length of neurofilament positive fibers and increased numbers of growth cone-like structures around the lesion *** human umbilical cord mesenchymal stem cells survived,migrated over short distances,and produced large amounts of glial cell line-derived neurotrophic factor and neurotrophin-3 in the host spinal *** were fewer reactive astrocytes in both the rostral and caudal stumps of the spinal cord in the human umbilical cord mesenchymal stem cell group than in the control *** Treatment with hum

关键词： functional recovery mesenchymal stem cells spinal cord injury transplantation umbilical cord

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