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Science china(Life sciences) 2010年第3期53卷 315-321页

作者： luo zhenge institute of neuroscience and state key laboratory of neuroscience,shanghai institutes for biological sciences,chinese academy of sciences,shanghai 200031,china institute of neuroscience and state key laboratory of neuroscience Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai China

Synapses are specialized structures that mediate information flow between neurons and target cells,and thus are the basis for neuronal system to execute various functions,including learning and memory.There are around 1011 neurons in the human brain,with each neuron receiving thousands of synaptic inputs,either excitatory or inhibitory.A synapse is an asymmetric structure that is composed of pre-synaptic axon terminals,synaptic cleft,and postsynaptic compartments.Synapse formation involves a number of cell adhesion molecules,extracellular factors,and intracellular signaling or structural proteins.After the establishment of synaptic connections,synapses undergo structural or functional changes,known as synaptic plasticity which is believed to be regulated by neuronal activity and a variety of secreted factors.This review summarizes recent progress in the field of synapse development,with particular emphasis on the work carried out in china during the past 10 years(1999-2009).

关键词： synapse development neuronal activity synaptic plasticity

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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）...

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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： Cai-Yun DENG~(**),Xiao-Hui XU~(**),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

＜正＞The formation of axons and dendrites and maintenance of the neuron’s vastly expanded surface require the continuous addition of new membrane.During 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 cone.Previously we have found the involvement of Rab10 in directional membrane insertion of plasmalemmal precursor vesicles（PPV） during neuronal polarization.However the mechanism of Rab10 action remains unknown.Here we report that the myristoylated alanine-rich C kinase substrate（MARCKS） interacts with Rab10 and mediates fusion of PPV to the plasma membrane.Down-regulation of MARCKs using siRNA against MARCKS abrogated polarized distribution of Rab10 and prevented neuronal polarization.Furthermore, blockade of the interaction between Rab10 and MARCKS by over-expressing the MARCKS domain that mediated the RablO-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 signals.Finally,blocking the interaction between Rab10 and MARCKS inhibited axon growth in vitro and in vivo.Thus,Rab10 interaction with MARCKS mediates fusion of PPV with the plasma membrane,a process required for axonal growth.

关键词： MARCKS Rab10 plasmalemmal precursor vesicle axonal growth fusion membrane insertion

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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）...

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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

＜正＞The formation of axons and dendrites and maintenance of the neuron’s vastly expanded surface require the continuous addition of new membrane.During 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 cone.Previously we have found the involvement of Rab10 in directional membrane insertion of plasmalemmal precursor vesicles（PPV） during neuronal polarization.However the mechanism of Rab10 action remains unknown.Here we report that the myristoylated alanine-rich C kinase substrate（MARCKS） interacts with Rab10 and mediates fusion of PPV to the plasma membrane.Down-regulation of MARCKs using siRNA against MARCKS abrogated polarized distribution of Rab10 and prevented neuronal polarization.Furthermore, 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 signals.Finally,blocking the interaction between Rab10 and MARCKS inhibited axon growth in vitro and in vivo.Thus,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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Rab5 dependent membrane endocytosis is required for Semaphorin3A induced axon growth cone collapse

Rab5 dependent membrane endocytosis is required for Semaphor...

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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： Kong-Yan WU~1,Ai-Li SHENG~1,Wen-Wen LIU~2,An-Qi GENG~1,Xing-Yu JIANG~2,Xiao-Bing YUAN~1, Zhen-Ge luo~(1,*) 1 institute of neuroscience,state key laboratory of neuroscience,shanghai institutes for biological sciences,chinese academy of sciences,shanghai 200031,china 2 CAS key Lab for biological Effects of Nanomaterials and Nanosafety,National Center for NanoScience and Technology,Beijing 100190,china

＜正＞Guidance cues are critical for axon navigation and ultimately for the wiring of the neuro-circuits during nervous system development.Growth cones of growing axons can sense both attractive and repulsive cues in the environment and make a corresponding response.Semaphorin3A,a negative guidance cues,can collapse growth cones of outgrowing axons,however,the intracellular molecular mechanisms are not well understood.Here we show that the small GTPase Rab5 is involved in growth one collapse in response to Semaphorin3A.Rab5 activity assay shows that Rab5 is transiently activated after treatment with Semaphorin3A.Growth cone collapse is abolished by down-regulation of Rab5 by specific siRNA in response to semaphorin3A.Taking advantage of live cell FRET assay,we demonstrate that semaphorin3A can activate Rab5 and promote the retrograde trafficking of Rab5 positive endosomes in growth cones.Rab5 is required for endocytosis of the growth cone plasma membrane during growth cone collapse. Over-expression of Rab5 leads to axon growth cones collapse in vitro and impedes projecting axons growth in vivo. These findings indicate that in response to negative guidance molecules semaphorin3A,axon growth cones driving endocytosis of the plasma membrane associated with the activated function of Rab5 resulted in growth cone collapse.

关键词： growth cone Semaphorin3A Rab5 endocytosis plasma membrane FRET microfluidic culture system electroporation

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Nurrl is essential for the differentiation of DA neurons during zebrafish embryogenesis

Nurrl is essential for the differentiation of DA neurons dur...

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中国神经科学学会第四次会员代表大会暨第七届全国学术会议

作者： Guang-Rui luo,Yi CHEN,Xu-Ping LI,Ting-Xi LIU~*,Wei-Dong LE~* institute of Health sciences,shanghai institutes for biological sciences,chinese academy of sciences and shanghai Jiao Tong University School of Medicine,200025,shanghai,china state key laboratory for Medical Genomics, RuiJin Hospital,Jiao Tong University School of Medicine,200025,shanghai,china institute of Neurology,RuiJin Hospital,Jiao Tong University School of Medicine,200025,shanghai.china odel Organism Division E-institutes of shanghai Universities,shanghai,china

＜正＞Nurrl has been recently found to be critical for the development and maintenance of mesencephalic dopamine （DA） neurons.To uncover the molecular mechanisms by which Nurr 1 contributes to the development of DA neurons,we have applied zebrafish to study the topographic distribution of nurrl transcripts during the early embryogenesis because of its ectogenesis and transparent,as well as its correlation with neuron progenitor marker（ngn1） and DA neuron markers （tyrosine hydroxylase,TH and DA transporter,DAT）.Our studies show that although nurrl transcripts did not co-localize with TH and DAT transcripts in the basal forebrain,it partially co-expressed with ngn1 in the region before 36 hpf. Knockdown of Nurr1 resulted in significant decrease of TH+ and DAT+ DA neurons,accompanied by reduction of DA transmitter and locomotive activities.Decreased number of DA neurons and reduced DA transmitter in Nurr1-deficient embryos were significantly rescued by the injection of mouse Nurrl mRNA.Surprisingly,the number of nurrl + cells in Nurr1-deficient embryos was increased by 1.6 fold.These results suggest that Nurrl plays a crucial role in the differentiation and maturation rather than the survival of DA progenitors during zebrafish early embryogenesis.

关键词： nurr1 DA progenitors and zebrafish

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Different neurotropic pathogens elicit neurotoxic CCR9-or neurosupportive CXCR3-expressing microgli

Different neurotropic pathogens elicit neurotoxic CCR9-or ne...

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中国免疫学会第五届全国代表大会暨学术会议

作者： Zhou Gang, He Yu-ling, He Li, Xie luo-kun , Xiong Jie, Lei Hao, Wei Li, Hu Chun-song, Liu Jun-yan, Jian Ming-shen, Jin You-xin, Gong Fei-li, Jin Bo-quan, Tan Jin-quan Departments of Immunology Parasitology, institute of Allergy and Immune-related Diseases Laboratories of neuroscience Allergy and Clinical Immunology, Center for Medical Research, Wuhan University School of Medicine, Wuhan The state key laboratory of Molecular Biology and neuroscience, institute of Biochemistry and Cell Biology, shanghai institutes for biological sciences, chinese academy of Science, shanghai The state key laboratory of Magnetic Resonance and Atomic and Molecular Physics, institute of Physics and Mathematics, chinese academy of sciences, Wuhan key laboratory of Colloid, Interface Science and Chemical Thermodynamics, institute of Chemistry, chinese academy of sciences, Beijing Department of Immunology, College of Basic Medical sciences, Anhui Medical University, Hefei Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan Department of Immunology, Fourth Military Medical University, Xian, P. R. china

What mechanism to determine microglia accomplishing destructive or constructive role in CNS remains nebulous. We report here that intracranial priming and re-challenging with T. gondii in mice elicit neurotoxic CCR9+ Irg1+(immunoresponsive gene 1) microglia, which are resistant to apoptosis and produce high level of TNF-α;priming and re-challenging with LCMV (lymphocytic choriomeningitis virus) elicit neurosupportive CX-CR3+ Irg1- microglia, which are sensitive to apoptosis and produce high level of IL-10 and TGF-β. Administration of CCR9 or/and Irgl siRNAs alters the frequency and functional profiles of neurotoxic CCR9+ Irg1+ and neurosupportive CXCR3 +Irg1- microglia in vivo. Moreover, by using a series of different neurotropic pathogens including intracellular parasites, chronic virus, bacteria, toxic substances, and CNS injury to intracranially prime and subsequent re-challenge mice, the bi-directional elicitation of microglia has been confirmed as neurotoxic CCR9+ Irg1+ and neurosupportive CXCR3+ Irg1- cells in these mouse models. These data suggest that there exist two different types of microglia, providing with a novel insight into microglial involvement in neurodegenerative and neuroinflam-matory pathogenesis such as Alzheimer s disease and AIDS dementia.

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The regulatory mechanism of autophagy of development of the nervous system

The regulatory mechanism of autophagy of development of the ...

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中国神经科学学会第十二届全国学术会议

作者： Xianli Wang zhenge luo institute of neuroscience State Key Laboratory of Neuroscience Shanghai Institutes for Biological Sciences Chinese Academy of Sciences chinese academy of sciences University CAS Center for Excellence in Brain Science and Intelligence Technology shanghaiTech University

Autophagy is a conserved, intracellular, lysosomal degradation pathway. While mechanistic aspects of this pathway are increasingly well defined, it remains unclear how autophagy modulation impacts normal physiology. It is, however, becoming clear that autophagy may play a key role in regulating developmental pathways. Here we describe how autophagy impacts neural stem cell differentiation. We define a novel route whereby this plasma membrane-resident receptor is degraded by autophagy, via uptake into ATG5-positive autophagosome-precursor vesicles. We extend our findings using a physiologically relevant mouse model with a hypomorphic mutation in Atg5, a crucial autophagy gene, which shows developmental retention but the differentiation of stem cells is accelerated and thus reveal how modest changes in autophagy can impact stem cell fate. This may have relevance for diverse disease conditions, like Alzheimer’s disease or Crohn’s Disease, associated with altered autophagy.

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Non-apoptotic role of caspase-3 in synapse ref inement

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neuroscience Bulletin 2014年第4期30卷 667-670页

作者： Jin-Yuan Wang Zhen-Ge luo institute of neuroscience State Key Laboratory of NeuroscienceShanghai Institutes for Biological SciencesChinese Academy of Sciences

Caspases, a family of cysteine proteases, mediate programmed cell death during early neural development and neurodegeneration, as well as following neurotoxic insults. Notably, accumulating lines of evidence have shown non-apoptotic roles of caspases in the structural and functional plasticity of neuronal circuits under physiological conditions, such as growth-cone dynamics and axonal/dendritic pruning, as well as neuronal excitability and plasticity. Here, we summarize recent progress on the roles of caspases in synaptic refinement.

关键词： caspases neuronal plasticity synaptic refinement

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Biomarkers of aging

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Science china(Life sciences) 2023年第5期66卷 893-1066页

作者： Aging Biomarker Consortium Hainan Bao Jiani Cao Mengting Chen Min Chen Wei Chen Xiao Chen Yanhao Chen Yu Chen Yutian Chen Zhiyang Chen Jagadish K Chhetri Yingjie Ding Junlin Feng Jun Guo Mengmeng Guo Chuting He Yujuan Jia Haiping Jiang Ying Jing Dingfeng Li Jiaming Li Jingyi Li Qinhao Liang Rui Liang Feng Liu Xiaoqian Liu Zuojun Liu Oscar Junhong luo Jianwei Lv Jingyi Ma Kehang Mao Jiawei Nie Xinhua Qiao Xinpei Sun Xiaoqiang Tang Jianfang Wang Qiaoran Wang Siyuan Wang Xuan Wang Yaning Wang Yuhan Wang Rimo Wu Kai Xia Fu-Hui Xiao Lingyan Xu Yingying Xu Haoteng Yan Liang Yang Ruici Yang Yuanxin Yang Yilin Ying Le Zhang Weiwei Zhang Wenwan Zhang Xing Zhang Zhuo Zhang Min Zhou Rui Zhou Qingchen Zhu Zhengmao Zhu Feng Cao Zhongwei Cao Piu Chan Chang Chen Guobing Chen Hou-Zao Chen Jun Chen Weimin Ci Bi-Sen Ding Qiurong Ding Feng Gao Jing-Dong JHan Kai Huang Zhenyu Ju Qing-Peng Kong Ji Li Jian Li Xin Li Baohua Liu Feng Liu Lin Liu Qiang Liu Qiang Liu Xingguo Liu Yong Liu Xianghang luo Shuai Ma Xinran Ma Zhiyong Mao Jing Nie Yaojin Peng Jing Qu Jie Ren Ruibao Ren Moshi Song Zhou Songyang Yi Eve Sun Yu Sun Mei Tian Shusen Wang Si Wang Xia Wang Xiaoning Wang Yan-Jiang Wang Yunfang Wang Catherine CL Wong Andy Peng Xiang Yichuan Xiao Zhengwei Xie Daichao Xu Jing Ye Rui Yue Cuntai Zhang Hongbo Zhang Liang Zhang Weiqi Zhang Yong Zhang Yun-Wu Zhang Zhuohua Zhang Tongbiao Zhao Yuzheng Zhao Dahai Zhu Weiguo Zou Gang Pei Guang-Hui Liu Aging Biomarker Consortium(ABC) Beijing 100101China CAS key laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China state key laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Department of Dermatology Xiangya HospitalCentral South UniversityChangsha 410008China Hunan key laboratory of Aging Biology Xiangya HospitalCentral South UniversityChangsha 410008China National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangsha 410008China Clinic Center of Human Gene Research Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Hubei Clinical Research Center of Metabolic and Cardiovascular Disease Huazhong University of Science and TechnologyWuhan 430022China Hubei key laboratory of Metabolic Abnormalities and Vascular Aging Huazhong University of Science and TechnologyWuhan 430022China Stem Cell Translational Research Center Tongji HospitalTongji University School of MedicineShanghai 200065China Department of Nuclear Medicine Daping HospitalThird Military Medical UniversityChongqing 400042China CAS key laboratory of Nutrition Metabolism and Food SafetyShanghai Institute of Nutrition and HealthUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200031China shanghai key laboratory of Maternal Fetal Medicine Clinical and Translational Research Center of Shanghai First Maternity and Infant HospitalFrontier Science Center for Stem Cell ResearchShanghai Key Laboratory of Signaling and Disease ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China The Department of Endovascular Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China key laboratory of Regenerative Medicine of Ministry of Education Institute of Ageing and Regenerative MedicineJ

Aging biomarkers are a combination of biological parameters to(i)assess age-related changes,(ii)track the physiological aging process,and(iii)predict the transition into a pathological status.Although a broad spectrum of aging biomarkers has been developed,their potential uses and limitations remain poorly characterized.An immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research:How old are we?Why do we get old?And how can we age slower?This review aims to address this need.Here,we summarize our current knowledge of biomarkers developed for cellular,organ,and organismal levels of aging,comprising six pillars:physiological characteristics,medical imaging,histological features,cellular alterations,molecular changes,and secretory factors.To fulfill all these requisites,we propose that aging biomarkers should qualify for being specific,systemic,and clinically relevant.

关键词： aging senescence biomarker clock

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HOPX and HOPX epressed cells study in mouse development cortex

HOPX and HOPX epressed cells study in mouse development cort...

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中国神经科学学会第十二届全国学术会议

作者： Qi Xiao Xiang-Chun Ju Zhen-Ge luo institute of neuroscience State Key Laboratory of Neuroscience Shanghai Institutes for Biological Sciences Chinese Academy of Sciences University of chinese academy of sciences Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of Sciences

Objective In recent years, discovery of human outer sub-ventricle zone（OSVZ） which was populated with non-epithelial radial glia-like cells attracted a wide spread attention. And HOPX also frequently regarded as trustable o RG markers in recent study about human neocortex or cultured organoid. However HOPX is not human-specific gene and it also has prevalent expression mainly at VZ and cortical hem in rodent cortex. It’s conflict with the fact that o RG cells existed in mouse only one in a million. Thus the cell type and differentiation fate of HOPX expressed cells and the function of HOPX remains to be further study. Methods We trying to trace the HOPX expressed cells in mouse to define which differentiation fate they may choose in the end, also exploring the function of HOPX by in utero electroporation in vivo and knockdown in vitro in this research simultaneously. Results（1） HOPX has prevalent expression pattern in VZ/SVZ of septal and ventral cortex, and cells expression level of HOPX is related to ultimate differentiate fate. Furthermore, Lineage tracing shows that cells higher expressed HOPX more likely to go through gliogenesis rather than neurogenesis.（2）HOPX expressed cells also generate Olig2 positive oligodendrocyte cells in mouse corpus callosum and neocortex.（3） HOPX knockdown in VZ/SVZ of mouse development cortex gives rise to misdistribution of GFP positive cells, this consequence remind us that HOPX may also take effect in neurogenesis of radial glia despite its very low expression level.

关键词： HOPX oligodendrocyte gliogenesis development cortex

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