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Membrane insertion of plasmalemmal precursor vesicles(PPV) is mediated by RablO interaction with MARCKS during axonal growth

Membrane insertion of plasmalemmal precursor vesicles(PPV) 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： Xiao-Hui XU~#,Cai-Yun DENG~#,Yang LIU,Tong WANG,Zhen-Ge LUO~* Institute of Neuroscience and State Key Laboratory of Neuroscience,Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences,Shanghai 200031,China

The formation of axons and dendrites and maintenance of the neuron's vastly expanded surface require the continuous addition of new *** axon extension,the coordination of membrane traffic,adhesion to extracellular substrate,and reorganization of the cytoskeleton at the peripheral region of the growth cone mediate the protrusive activity of the axon growth *** we have found the involvement of Rab10 in directional membrane insertion of plasmalemmal precursor vesicles(PPV) during neuronal *** the mechanism of Rab10 action remains *** we report that the myristoylated alanine-rich C kinase substrate(MARCKS) interacts with Rab10 and mediates fusion of PPV to the plasma ***-regulation of MARCKs using siRNA against MARCKS abrogated polarized distribution of Rab10 and prevented neuronal ***, blockade of the interaction between Rab10 and MARCKS by over-expressing the MARCKS domain that mediated the Rab10-MARCKS binding abolished membrane fusion of PPVs,which were labeled with BODIPY-ceramide. Membrane fusion of PPVs was also measured by analyzing the TIRF(Internal Reflection Fluorescence) signals of pHluorin-tagged receptors of axon growth promoting factors - TrkB for brain-derived neurotrophic factor(BDNF) and IGFR for insulin like factor 1(IGF-1).We found that down-regulation of MARCKS or blocking its interaction with Rab10 inhibited the TIRF ***,blocking the interaction between Rab10 and MARCKS inhibited axon growth in vitro and in ***,Rab10 interaction with MARCKS mediates fusion of PPV with the plasma membrane,a process required for axonal growth.

关键词： MARCKS RablO plasmalemmal precursor vesicle axon growth docking fusion

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Perivascular distribution of aquaporin 4 is modulated by electroacupuncture in ischemic rat brain

Perivascular distribution of aquaporin 4 is modulated by ele...

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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： Fan YANG,Qing-Xiao REN,Chang-Peng WANG,Min ZHU,Jing-Chun GUO~* State Key Laboratory of Medical Neurobiology,Shanghai Medical College of Fudan University,Shanghai 200032, China

Objective Brain edema is an associated complication of stroke *** demonstrated that aquaporin 4(AQP4) plays key roles in the process of cerebral edema formation and *** previous study showed that electroacupuncture(EA) significantly alleviates post-ischemic edema,and prevents ischemia-induced upregulation of AQP4 mRNA ***,mechanisms responsible for ischemic edema reduction by EA treatment still remain *** present study was to investigate whether the AQP4 protein expression and distribution is involved in the anti-edema protective effect of *** Focal cerebral ischemia was induced by middle cerebral artery occlusion in adult *** was delivered to acupoints Baihui(GV 20) and Renzhong(GV 26) immediately after ischemia ***4 protein expression and poloarized distribution were assessed by western blot and pre-embedding immunogold labeling,***(1) EA reduces ischemia-induced upregulation in AQP4 protein expression in the early stage of ischemia/reperfusion injury.(2) EA alters perivascular localization of AQP4 protein at 6 h and 24 h of reperfusion after 1 h ischemia.(3) EA reduces ischemic infarction and brain swelling, and improves neurological behavior after focal cerebral ischemia/reperfusion *** EA dynamically modulates the perivascular distribution of AQP4 in ischemic *** effects may be involved in the beneficial effects of EA in reducing ischemic edema and infarction,and thereafter,improving neurological outcome.

关键词： stroke middle cerebral artery occlusion edema electroacupuncture aquaporin 4

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Regulation of intracellular manganese hemeostasis by Kufor-Rakeb syndrome associated ATP13A2

Regulation of intracellular manganese hemeostasis by Kufor-R...

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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： Jie-Qiong TAN~1,Tong-Mei ZHANG~1,Li JIANG~2,Jing-Wei CHI~1,Dong-Shen HU~2,Qian PAN,Dan-Ling WANG~1, Zhuo-Hua ZHANG~(1,3,*) 1 State Key Laboratory of Medical Genetics,Central South University,Changsha 410078,China 2 Nanhai Entry-Exit Inspection and Quarantine Bureau,Foshan 528200,China 3 Burnham Institute for Medical Research,La Jolla,CA 92037,USA

Mutations in ATP13A2 gene are associated with Kufor-Rakeb syndrome and are also found in patients with various types of ***13A2 encodes a predicted lysosomal P5-type ATPase that plays important roles in regulating cation *** of cation homeostasis in brain has been indicated in PD pathogenesis. In the present study,we explored the biological function of ATP 13A2 as well as the pathogenic mechanism of the KRS pathogenic ATP13A2 *** revealed that wild-type ATP13A2,but not the KRS-associated ATP13A2 mutants,protected cells from Mn-induced cytotoxicity in mammalian cell lines and primary rat neuronal cultures. Meanwhile,wild-type ATP13A2 reduced intracellular manganese concentration and prevented cytochrome c release from mitochrontria in a Mn overload model compared to the pathogenic ***,mRNA level of endogenous ATP13A2 was upregulated with Mn *** results suggest that ATP13A2 plays important roles in protecting cells against manganese cytotoxicity via regulating intracellular manganese *** study provides a potential mechanism of KRS and parkinsonism.

关键词： Kufor-Rakeb syndrome ATP13A2 manganese

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Functional roles of Mst3 in radial migration during the development of mouse cerebral cortex

Functional roles of Mst3 in radial migration during the deve...

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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： Jacque P K IP Amy K Y FU Nancy Y IP Division of Life Science State Key Laboratory of Molecular Neuroscience and Molecular Neuroscience CenterThe Hong Kong University of Science and TechnologyClear Water Bay

＜正＞Objective Radial migration is critical for the lamination of cerebral cortex during early brain development. Whereas the migration of neurons requires a precise regulation of the organization and dynamics of cytoskeleton including microtubule and actin network,the underlying signaling mechanisms are not well *** the present study,we investigate the functional roles of a kinase Mst3 in radial migration during cortical *** The radial migration in mouse neocortex was investigated by in utero *** cone collapse assay in cultured hippocampal neurons was performed using confocal ***（1） We identified that Mst3, a serine/threonine kinase highly expressed in the developing mouse brain,regulates the neuronal differentiation. （2） Silencing of Mst3 by in utero electroporation resulted in a significant delay on the neuronal migration in the developing mouse neocortex.（2） Kinase activity of Mst3 was essential for its functions in neuronal morphogenesis and migration.（3） Mst3 was co-localized with F-actin at the growth cones of cultured hippocampal neurons,and regulated actin *** Kinase activity of Mst3 is important for neuronal morphogenesis and radial migration through modulation of actin dynamics.

关键词： mammalian Sterile 20-like kinase 3 Mst3 neuronal migration actin dynamics

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Facilitating synaptic transmission of (-)clausenamide in CA1 region of hippocampal slices by activating CaMKIIa

Facilitating synaptic transmission of (-)clausenamide in CA1...

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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： Jin-Feng HU,Na Ning,Yu-He YUAN,Jun-Tian ZHANG,Nai-Hong CHEN~* Key Laboratory of Bioactive Substances and Resources Utilization,Ministry of Education,Department of Pharmacology,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China

Objective Effect of(-)clausenamide on potentiating field excitatory postsynaptic potential(f-EPSP)in CA1 region of rats' hippocampal slice and its related mechanism were investigated in the *** 8×8 multi-electrode array probe was used to measure *** phosphorylation and expression of CaMKIIα,ERK1/2, CREB were detected by Western ***(-)Clausenamide facilitated synaptic plasticity at dose-dependent ***(-)clausenamide also activated CaMKIIa and ERK1/*** with KN93(CaMKIIa inhibitor, 10μM)for 20 min before(-)clausenamide addition completely blocked the enhancement of synaptic transimisson induced by(-)***98059(MEK inhibitor,30μM)partially blocked the effect of(-)*** KN93 and PD98059 attenuated the activation of CREB induced by(-)***,the results suggested that CaMKIIα-ERKl/2-CREB involved in the process of(-)clausenamide facilitating synaptic transmission.U73122,an inhibitor of PLCγ,attenuated the slop of f-EPSP before or after the treating of(-)*** blocked partially the effect of(-)clausenamide by pre-incubation,but showing no difference with basic value when treated after the perfusion of(-)*** data indicated that external calcium influx induced by(-)clausenamide was necessary for initiating synaptic transmission and calcium influx induced by(-)clausenamide may promote the release of intracellular calcium responsible for synaptic ***(-)clausenamide promoted calcium influx to initiating synaptic transmission and triggering intracellular calcium release,and subsequently activated CaMKIIα-ERK1/2 -CREB signal pathway.

关键词： (-)clausenamide synaptic transmission CaMKIIα calcium

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Human auditory cortex activity shows additive effects of spectral and spatial cues during speech segregation

Human auditory cortex activity shows additive effects of spe...

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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： Bernhard ROSS Tim BARDOUILLE Claude ALAIN Department of Psychology University of TorontoOntarioM8V2S4Canada

Introduction In noisy social gatherings,listeners perceptually integrate sounds originating from one person's voice(e.g.,fundamental frequency（f） and harmonics) at a particular location and segregate these from concurrent sounds of other *** increasing either the spectral（e.g.,f） or the spatial distance between talkers promotes speech segregation,the synergetic effect of having more than one cue available is less well *** We studied how spectral and/or spatial distances between 2 simultaneously presented steadystate vowels contribute to participants' perception（accuracy of both vowels） and activation in auditory cortex using magnetoencephalography（MEG）.Results Participants were more accurate in identifying both vowels when they differed in f and location than when they differed in a single cue only or when they shared the same f and location. The combined effect of f and location differences closely matched the sum of single *** improvement in concurrent vowel identification coincided with an object-related negativity（ORN） that peaked at about 140 ms after vowel *** combined effect of f and location on dipole source waveforms closely matched the sum of single effects even though vowels with different f,location,or both,generated different time courses of neuromagnetic *** model-free beamforming analysis provided converging evidence for summation of f and location cues in auditory cortices during speech *** We propose that during auditory scene analysis,acoustic differences among the various sources are combined linearly to increase the perceptual distance between the cooccurring sound objects.

关键词： MEG speech attention scene analysis streaming

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Fruit flies-in vivo screening models for Alzheimer's and other CNS diseases

Fruit flies-in vivo screening models for Alzheimer's and oth...

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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： Weiwei MA~1,I-Feng PENG~1,Yi ZHONG~(1,2,3,*) 1 Suzhou JoeKai Biotech LLC,Suzhou 215300,China 2 School of Life Science,Tsinghua University,Beijing 100084,China 3 Cold Spring Harbor Laboratories,Long Island,NY,11724,USA

In current drug discovery pipeline,in vitro biochemical and cell-based screening assays have been widely used before the validation tests in in vivo animal ***,the gap between two platforms sometimes impairs the discovery progress,especially for the diseases with complicated *** order to minimize such gap in the CNS disease area,we have developed several Drosophila models as supplementary approaches in parallel to the in vitro *** CNS fly models preserve behavioral deficits and pathological hallmarks similar to those observed in human patients,yet are low in running cost and are suitable for high-throughput screening *** fly Alzheimer's disease(AD) model was generated through targeted pan-neuronal expression of a transgene encoding a secretive form of human Aβ42 peptides in the Drosophila *** expression leads to neurodegeneration with accumulation of Aβ42 and fibril deposits in the brain area,which may lead to shortened life *** addition,AD flies also display severe age-dependent memory loss,highly mimicking dementia syndrome in AD ***-controlled massive screening devices were utilize in the fly memory(T-maze) system,enabling screening of hundreds of compounds per day in scale for industrial *** model for NFl,Noonan syndrome were developed for drug screening service,along with other CNS disease models such as Parkinson's disease(PD),schizophrenia,and autism that have also been planned for the pipelines in CNS drug discovery.

关键词： Alzheimer Fruit flies-in vivo screening models for Alzheimer's and other CNS diseases CNS

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Oxidative stress and NAD+ in ischemic brain injury

Oxidative stress and NAD+ in ischemic brain injury

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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： Wei-Hai YIN~* Neuroscience and Neuroengineering Research Center,Med-X Research Institute,Shanghai Jiao Tong University, Shanghai 200030,China

Numerous studies have indicated oxidative stress as a key pathological factor in ischemic brain *** of the key links between oxidative stress and cell death is excessive activation of poly(ADP-ribose) polymerase-1 (PARP-1),which plays an important role in the ischemic brain damage in male *** studies have also suggested that NAD+ depletion mediates PARP-1 cytotoxicity,and NAD+ administration can decrease ischemic brain injury.A number of recent studies have provided novel information regarding the mechanisms underlying the roles of oxidative stress and NAD+-dependent enzymes in ischemic brain *** particular interest,there have been exciting progresses regarding the mechanisms underlying the roles of NADPH oxidase and PARP-1 in cerebral *** examples,it has been suggested that androgen signaling and binding of PARP-1 onto estrogen receptors could account for the intriguing findings that PARP-1 plays remarkably differential roles in the ischemic brain damage of male and female animals;and some studies have suggested casein kinase 2,copper-zinc superoxide dismutase, and estrogen signaling can modulate the expression and activity of NADPH *** review summarizes these important current advances,and proposes future perspectives for the studies on the roles of oxidative stress and NAD+ in cerebral *** is increasingly likely that future studies on NAD- and NADP-dependent enzymes,such as NADPH oxidase,PARP-1,and sirtuins,would expose novel mechanisms underlying the roles of oxidative stress in cerebral ischemia,and suggest new therapeutic strategies for treating the debilitating disease.

关键词： Oxidative stress and NAD in ischemic brain injury

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MicroRNA-21 stimulates neurite growth by targeting paired-like homeodomain 2 following sciatic nerve injury

MicroRNA-21 stimulates neurite growth by targeting paired-li...

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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： Song-Lin ZHOU,Deng-Bing YAO,Yong-Jun WANG,Xiao-Song GU,Fei DING~* Jiangsu Key Laboratory of Neuroregeneration,Nantong University,Nantong 226001,China

Objective Nerve regeneration is a complex biological phenomenon incorporating multiple cells,growth factors and an extracellular *** are endogenous,non-coding 21-to 23-nucleotide small RNA molecules that regulate gene expression by binding to the 3' untranslated region of target mRNAs,leading to their translational inhibition or *** present study is to explore whether miRNAs are capable of mobilizing the intrinsic capacity for neurite growth and promoting axon *** We analyzed the changes in miRNA and mRNA expression in the DRG,following sciatic nerve transection,using microarray and bioinformatics *** validate the microarray platform,we assessed the expression by real time Taqman *** validate the target,we performed luciferase reporter ***,we transfected the miRNA-21 mimics and PITX2 siRNA to the cultured DRG ***(1)The bioinformatics analysis indicated that miRNA-21 play important roles in regulating nerve regeneration via the target PITX2 in the network.(2)miRNA-21 is inversely correlated with PITX2 expression in DRG tissues.(3)In the cultured DRG neurons,miRNA-21 promotes neurite growth and inhibits PITX2 expression. Transfection of PITX2 siRNA also promotes neurite *** miRNA-21 is significantly up-regulated following sciatic nerve injury and promotes neurite growth by targeting PITX2.

关键词： nerve regeneration miRNA-21 PITX2 DRG

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Role of KCC2 in seizure induction and intervention

Role of KCC2 in seizure induction and intervention

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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： Yun WANG Institutes of Brain Science and State Key Laboratory for Medical Neurobiology,Fudan University,Shanghai 200032, China

The neuron specific K-Cl cotransporter KCC2 in adult plays an important role to maintain intracellular Cl homeostasis,hence renders GABA receptor inhibitory ***,KCC2 expression levels are found to be reduced in various pathological conditions,including *** current study,we analyzed KCC2 expression and function and its involvement in GABA receptor mediated inhibition change during acute seizure *** using cyclothiazide（CTZ） induced both in vivo and in vitro acute seizure model,we discovered that the hippocampal neuron somatic membrane KCC2 expression was down regulated,the GABA reversal potential(E) was up- shifted and a profound reduction in Cl extrusion *** molecular manipulation of KCC2 expression in cultured hippocampal neurons,CTZ treatment induced epileptic neurons was significantly reduced in association with KCC2 over expression,and KCC2 down regulated by shKCC2 resulted a E up-shift but without effect on CTZ induction of epileptiform *** addition,furosemide,a KCC2 inhibitor,while applied continuously mimicked CTZ effect to cause the E up-shift and facilitate the CTZ induced epileptiform ***,furosemide co-treated with CTZ prevented CTZ induced KCC2 down regulation from the somatic membrane and in turn rescued acute convulsant stimulation induced GABA inhibitory function *** conclusion,our data suggest that KCC2 plays an important role in seizure induction and prevent KCC2 down regulation may be a novel target for anticonvulsant development.

关键词： CTZ epilepsy hippocampus KCC2 GABAA receptor

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