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Parkin ameliorates dopaminergic neurodegeneration induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine through protection of mitochondria and reduction of a-synuclein in the nigrostriatal pathway

Parkin ameliorates dopaminergic neurodegeneration induced by...

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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： Minjuan BIAN~#,Jie LIU~#,Xiaoqi HONG~#,Yufang HUANG,Mei YU,Yanlong HONG,Lihe GUO,Zhejin SHENG, Jian FEI,Fengyan SUN,Fang HUANG~* National Key Laboratory of Medical Neurobiology,Shanghai Medical College,Fudan University,Shanghai 200032, China

Mutations in the parkin gene are currently thought to be the most common cause of familial Parkinsonism. Overexpression of parkin has been reported to prevent neuronal degeneration under various *** generated a transgenic mouse model in which expression of wild type parkin was driven by neuron specific enolase promoter. Parkin transgenic mice exhibited less reduction of striatal TH protein and number of TH positive neurons in the substantia nigra induced by l-Methyl-4-Phenyl-l,2,3,6-Tetrahydropyridine(MPTP).Such a phenomenon was especially more obvious in old transgenic ***-induced mitochondrial impairment in the substantia nigra pars compacta was improved in parkin transgenic mice accompanied by elevated transcriptional expression of bcl-2 and *** striatal a-synuclein accumulation was shown in old parkin transgenic mice,however,striatal Hsp70 expression revealed no significant changes within groups in both young and old *** results provide the first mammalian genetic evidence that overexpression of parkin may attenuate dopaminergic neurodegeneration induced by MPTP through protection of mitochondria and reduction of a-synuclein in the nigrostriatal pathway.

关键词： parkin MPTP mitochondria a-synuclein Parkinson's disease

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Ionotropic glutamate receptors in medial prefrontal cortex and dorsal hippocampus are involved in different components of methamphetamineinduced conditioned place preference in mice

Ionotropic glutamate receptors in medial prefrontal cortex 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次会员代表大会

作者： Wen-Yan HAN~1,Fang WANG~1,Shi-Yuan FU~1,Ming SONG~2,Ping DU~1,Xiao-Long JING~1,Chun-Fu WU~(1,*),Jing-Yu YANG~(1,*) 1 Department of Pharmacology,Shenyang Pharmaceutical University,110016,Shenyang,China 2 Liaoning Institute of Crime Detectives,Shenyang 110032,China

Objective The medial prefrontal cortex(mPFC) and dorsal hippocampus(DHC) play significant roles in stimulant-induced neurobehavioral *** order to investigate the role of mPFC and DHC in methamphetamine (MAP) reward and drμg-priming induced relapse,the present study examined the effect of lesions of mPFC or DHC on the acquisition and MAP priming induced reinstatement of conditioned place preference(CPP) in *** After pre-training or establishment day of CPP,the animals received bilateral kainic acid(KA) or N-methyl-daspartate (NMDA) lesions of mPFC or *** The results showed that both KA and NMDA lesions of mPFC significantly blocked the acquisition of MAP-induced CPP,and a KA but not NMDA lesion of the DHC prevented the acquisition of MAP-induced ***,the MAP priming induced CPP-reinstatement was prevented by a KA but not NMDA lesion of mPFC,and was markedly inhibited by only an NMDA lesion of *** These findings indicated that the ionotropic glutamate receptors(iGluRs) in mPFC and DHC were involved in MAP-induced ***,different types of iGluRs in these two regions may be participated in acquisition and MAP-priming induced reinstatement of CPP,respectively.

关键词： methamphetamine conditioned place preference medial prefrontal cortex dorsal hippocampus kainic acid N-methyl-d-aspartate

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Kinetics of vesicle reuse at the Calyx of Held synapses

Kinetics of vesicle reuse at the Calyx of Held synapses

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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： Xu-Feng QIU,Qian-Wen ZHU,Jian-Yuan SUN~* Institute of Biophysics,Chinese Academy of Sciences,State Key Laboratory of Brain and Cognitive Science,Beijing 100101,China

Vesicle recycling and reuse is essential in maintaining synaptic *** spite of accumulative studies,it remains elucidated that how many vesicles involve in recycling,how long and how fast a vesicle can be reused after *** made the whole cell recording of the excitatory postsynaptic currents（EPSCs）at a central synapse,the Calyx of Held,under the long duration of stimulation in the presence of folimycin,a vesicular ATPase inhibitor to annihilates the H gradient and block glutamate refilling of synaptic *** was confirmed that vesicles at the Calyceal synpases do recycle and reuse after *** long trains of 20 Hz or 50 Hz stimulation,the evoked EPSCs can be rapidly depressed and finally mostly vanished,implying the depletion of the recycling *** size of the recycling pool was thus estimated as 180,000-350,000 *** did not observe the rapid vesicle reuse within 10 s,which supports the notion that rapid endocytosis does not immediately recycle vesicles within the readily releasable *** comparison between stimulation evoked EPSCs with and without folimycin,we further described the kinetics of synaptic vesicle reuse with double exponential *** from the previous ways to predict and estimate the kinetics of vesicle recycling by endocytotic kinetics,this study proposed a quantitatively description of the kinetics of synaptic vesicle reuse at a central synapse based on direct *** further proposed two pathways of synaptic vesicle recycling with distinguished kinetics.

关键词： vesicle recycling reserve pool,readily releasable pool

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Identification of an adenylyl cyclase inhibitor for treating neuropathic and inflammatory pain

Identification of an adenylyl cyclase inhibitor for treating...

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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： Susan S.KIM Kohei KOGA Giannina DESCALZI Kunjumon I.VADAKKAN Bong-Kiun KAANG Deparment of Physiology University of TorontoToronto M5S1A8Canada Institute of Neuroscience the Fourth Military medical UniversityXi'an 710032China

＜正＞Objective Neuropathic pain,often caused by nerve injury,is commonly observed among patients with different *** its basic mechanisms are poorly understood,effective medications are limited. Previous investigations of basic pain mechanisms and drug discovery efforts have focused mainly on early sensory neurons such as dorsal root ganglion and spinal dorsal horn neurons,and few synaptic-level studies or new drugs are designed to target the injury-related cortical plasticity that accompanies neuropathic *** previous work has demonstrated that calcium-stimulated adenylyl cyclase 1（AC1） is critical for nerve injury-induced synaptic changes in the anterior cingulate *** Rational drug design and chemical screening,a variety of behavioral tests, electrophysiological methods and toxicity studies were performed in the present *** It was identified that a lead candidate AC1 inhibitor,NB001,was relatively selective for AC1 over other adenylate cyclase ***001 has an analgesic effect in animal models of neuropathic pain,without any apparent side effects when administered intraperitoneally or *** AC1 could be a productive therapeutic target for neuropathic pain and describes a new agent for the possible treatment of neuropathic pain.

关键词： adenylyl cyclase anterior cingulate cortex neuropathic pain

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Stimulus specific adaptation in the cultured cortical network

Stimulus specific adaptation in the cultured cortical networ...

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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： Hai-Tao WANG,Yi-Fan HAN,Ju-Fang HE~* Applied Neuroscience Laboratory,Department of Rehabilitation Sciences,the Hong Kong Polytechnic University, Hong Kong,China

Stimulus specific adaptation(SSA)is widely demonstrated in many brain regions of human and intact animals from multiple spatial scales including extracellular units recording and *** models are proposed to explain that repetitive stimulus induces adaption of physiological responses to favor deviance stimulus detection in the network *** the present study,we would examine the SSA at the synapse level with whole cell patch clamp recording from the cultured cortical *** cultured pyramidal neurons shared the similar SSA properties in response to the odd-ball stimulation paradigm as those reported with in vivo *** different stimuli were from electrical stimulations that were spatially *** cultural neurons showed SSA to the electrical *** SSA was not attributable to a reduction of the intrinsic membrane properties in that cultured neurons faithfully followed the intracellular current injection up to 200 *** AMPA receptors mediated excitatory postsynaptic currents(EPSC)also displayed stronger SSA compared with the GABA receptors mediated inhibitory postsynaptic currents(IPSC).The different dynamic of short term synaptic depression characterized by EPSC and IPSC might account for the generation of SSA at the supra-threshold spike *** findings support that the synapse specific fatigue would be the candidate neural mechanism for the stimulus specific adaptation.

关键词： stimulus specific adaptation short term plasticity synaptically driven spikes EPSC IPSC

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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次会员代表大会

作者： W.C.CHAM D.K.Y.SHUM Departments of Biochemistry and Physiology LKS Faculty of Medicinethe University of Hong Kong

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 of hippocampal 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.

关键词： The role of proheparanase in synaptic plasticity of the hippocampus

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Endogenous expression of Neuregulin-1 as a potential modulator of prolactin secretion in GH3 cells

Endogenous expression of Neuregulin-1 as a potential modulat...

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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-Jiang ZHAO~(1,*),Song-Guang REN~2 1 Center for Neuroscience,Shantou University Medical College,Shantou,Guangdong Province 515041,China 2 Department of Medicine,Cedars-Sinai Medical Center,Los Angeles,California,USA

The binding of Nrgl to ErbB receptors mediates intercellular and intracellular communication,and it regulates a broad spectrum of biological processes,such as tumorigenesis and *** Nrgl has been shown to control prolactin(PRL)secretion from rat prolactinoma GH3 ***,the endogenous expression of Nrgl and its role in PRL secretion in GH3 cells are not *** this study,we demonstrate that typeⅢNrgl isoforms are endogenously expressed in GH3 *** in vitro functional analysis using siRNA against Nrgl revealed that endogenous Nrgl regulates PRL secretion from GH3 cells in part through an ErbB-3 receptor-dependent manner,with no significant effects on growth hormone(GH)***,Nrgl is a specific modulator of PRL secretion in GH3 ***,co-localization of Nrg1 and ErbB-2 receptor,which is shared by both ErbB- 3 and ErbB-4 receptors in the formation of heterodimers,was detected in one out of 5 human prolactinoma tissues. Our findings suggest that GH3 cells intrinsically express a group of typeⅢNrg1 isoforms that regulate PRL secretion through an autocrine/paracrine *** investigation into the role of Nrgl on PRL secretion may provide clues to advance the clinical management of prolactinoma.

关键词： Nrg1 GH3 cells prolactin autocrine-paracrine

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低频率电刺激海马下托对癫痫的作用研究及其机制初探

低频率电刺激海马下托对癫痫的作用研究及其机制初探

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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：钟恺许正浩汪仪徐层林吴登唱陈忠卫生部医学神经生物学重点实验室浙江大学医学部药理学系

目的前期研究发现,低频率电刺激（Low-frequency stimulation,LFS）特定脑区可以抑制癫痫。课题组近期发现,这种抑制作用可能存在一个非常短暂的"治疗时间窗"效应,即在癫痫后放电之后数秒内开始LFS才能抑制癫痫,其临床应用价... 详细信息

目的前期研究发现,低频率电刺激（Low-frequency stimulation,LFS）特定脑区可以抑制癫痫。课题组近期发现,这种抑制作用可能存在一个非常短暂的"治疗时间窗"效应,即在癫痫后放电之后数秒内开始LFS才能抑制癫痫,其临床应用价值有限,所以非常有必要寻找具有较长"治疗时间窗"效应的LFS刺激靶点。已有研究发现人类癫痫间期放电（～1 Hz）起始于海马下托,这种放电被认为具有抑制癫痫的作用。本研究利用LFS刺激海马下托,观察其是否具有抑制癫痫的作用,并初步探索其机制。方法和结果探讨不同时间点开始的LFS对大鼠杏仁核电点燃癫痫和锂盐匹罗卡品模型自发性癫痫的作用,并利用脑电位频谱分析手段,初步探讨其作用机制。在杏仁核电点燃癫痫模型中,癫痫诱发前LFS组（Pre组）、立即LFS组（Imm组）、后放电结束后LFS组（ADD-delayed组）与对照组相比,均能显著性抑制电点燃癫痫等级的进展,显著性缩短癫痫后放电持续时间;而且发现Double ADD-delayed组也能观察到抑制癫痫等级进展的作用;甚至在0.5 h后再给予LFS（0.5 h-delayed组）,仍能观察到其抑制癫痫后放电持续时间作用。同时我们还发现,给予0.5 Hz或者3 Hz的LFS对电点燃癫痫无抑制作用,提示LFS海马下托的抗癫痫作用存在1 Hz的频率特异性,其作用机制可能与海马下托1 Hz的间期放电有关。初步的频谱分析发现,杏仁核1Hz的能量随癫痫等级进展而上升,而LFS可能提前了这种能量上升的过程。在锂盐匹罗卡品模型中,每日两次LFS组能完全抑制癫痫自发发作;每日一次LFS组也能显著性推迟其首次癫痫自发发作出现的时间。结论 LFS海马下托能抑制大鼠杏仁核电点燃癫痫的形成过程和匹罗卡品诱发的自发性癫痫。海马下托具有较宽的LFS治疗时间窗,其作用机制不同于其他靶点,可能与其本身的1 Hz间期放电有关。海马下托可能是一个较有应用前景的LFS治疗靶点。

关键词：低频率电刺激海马下托杏仁核点燃锂盐匹罗卡品模型反复自发性癫痫

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The effect of electroacupuncture on expression of orexin and its receptors in the brain of chronic obstructive pulmonary disease rats

The effect of electroacupuncture on expression of orexin and...

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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： Zi-Bing LIU Wen-Ye GENG Na-Na SONG Li LI Yin-Xiang CAO Da-Nian ZHU Lin-Lin SHEN Anhui Provincial Key Lab of Acu-moxibustion Theoretical Foundation and Techniques Anhui College of Traditional Chinese Medicine Hefei 230038 China Department of Physiology and Pathophysiology Shanghai Medical College Fudan University Shanghai 200032 China Department of Physiology and Pathophysiology Shanghai Medical College Fudan University Shanghai 200032 China

Objective To investigate the relationship between acupuncture effects on improving pulmonary ventilatory function of chronic obstructive pulmonary disease (COPD) and hypothalamic neuropeptide *** (1) Sprague-Dawley rats were used to establish the COPD model by exposed to cigarette smoke (lh twice daily) for 12 weeks.(2) Model rats were electro-acupunctured on bilateral acupoints Feishu (BL13) and Zusanli (ST36) for 30 minutes a day for two weeks.(3) Hypothalamic and medullary orexinA levels were detected by radioimmunoassay, the orexin receptors' mRNA and positive immunoreactivity were observed by fluorescence realtime quantitative PCR and immunohistochemistry *** (1) The decrease of airway resistance and the increase of lung dynamic compliance in COPD model rats were occured after acupuncture treatment (P<0.05).(2) The orexinA level in hypothalamus and medulla was very higher in model group than that in normal group (P<0.01, P<0.001), but not significantly decreased in electro-acupuncture group.(3) mRNA and immune response positive expression of OX1R in ventrolateral medulla was significantly higher in the model group than those in the normal group (P<0.01), but mRNA and immune response positive expression of OX2R decreased significantly in the electro-acupuncture group compared with the model (P<0.01).Conclusion The effect of acupuncture for improving the pulmonary ventilatory function in COPD rats may be relevant to the down-regulation of neuropeptide orexin receptors' expression in medulla oblongata.

关键词： electro-acupuncture Feishu Zusanli chronic obstructive pulmonary disease orexin

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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-Ying MA Jing QIANG Ping GU Yan-Yong WANG Yuan GENG Ming-Wei WANG Brain aging and cognitive neuroscience laboratory of Hebei province shijiazhuang 050031 China Department of Neurology the frist hospital of Hebei Medical University shijiazhuang 050031 China

Objective Autophagy is responsible for the degradation of long-lived proteins and damaged organelles intracellular, even extracellular, and autophagy is proved to have relationship with Alzheimer's disease (AD) and *** senescence accelerated mouse prone 8 (SAMP8) was a non-genetically modified mice widely used as a rodent model of aging and senile ***, little was known about the age-related changes of autophagy in the brain of SAMP8 *** Transmission electron microscope was used to observe the age-related ultrastructure and AVs of hippocampal neurons in SAMP8 and SAMR1 *** used immunohistochemistry staining and Western-blot analysis to explore the ubiquitin-positive inclusion bodies, the expression of LC3 and Beclin 1 protein in different brain regions of SAMP8 and SAMR1 mice in 2, 7 and 12 months *** We found that 7 and 12-month-old SAMP8 mice presented cognitive decline and ubiquitinated proteins *** the hippocampal neurons of 12-month-old SAMP8 mice, lots of dense clumps and autophagic vacuoles were found in the cytoplasm and *** LC3-Ⅱ expression showed an increase in hippocampus and cortex of 7 and 12-month-old SAMP8 *** expression of Beclin 1 displayed a significant increase in 7 months old and a decline in 12 months *** Based on thesedata, we suggest that the autophagic activity maybe incease reactively at the beginning of AD and then showed a decline with aging, and the pathological changes of 12-month-old SAMP8 mice are more similar to the late-onset AD in the perspective of autophagy.

关键词： SAMP8 autophagy aging Alzheimer' s disease

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