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中国神经科学学会第十届全国学术会议

作者： Siqi LI Chunzhang YANG Zhengping ZHUANG albert cheung hoi yu Neuroscience Research Institute Department of NeurobiologySchool of Basic Medical SciencesPeking University Key Laboratory for Neuroscience Ministry of Education(Peking University) Key Laboratory for Neuroscience Ministry of National Health and Family Planning Commission(Peking University) Surgical Neurology Branch National Institute of Neurological Disorders and StrokeNational Institutes of Health Laboratory of Translational Medicine Institute of Systems BiomedicinePeking University

Mechanical injury of the brain has been studied for decades utilizing in vitro model of astrocytes,regarding to their remarkable cellular responses to the *** previous finding demonstrated that astrocytic beta-catenin plays fundamental roles in traumatic signal transduction and initiating cellular ***,it is still obscure about the details in molecular mechanism by which astrocytes initiate activation process and activate beta-catenin *** present study,we investigated the extracellular ligands mat trigger Wnt signal transduction during injury-associated astrocytic *** found that injury induced a global change in gene expression profile of Wnt family in *** injury-related Wnt production caused phosphorylation and internalization of Low-density lipoprotein receptor-related protein 6（Lrp6）,a co-receptor of canonical Wnt ***,Lrp6 was recruited into Axin/APC/GSK3beta degradation complex after injury,suggesting Lrp6 inhibits the degradation process of *** further demonstrated that the activation of Lrp6 is essential for astrocytic activation,since siRNA silencing of Lrp6 resulted in enhanced beta-catenin degradation and attenuated wound healing *** summary,we demonstrated that canonical Wnt signaling pathway was activated to inhibit beta-catenin degradation in astrogliosis and mediates the cellular activation of astrocytes.

关键词： astrocyte mechanical injury beta-catenin Wnt Lrp6

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Nucleic acid-based diagnostics for infectious diseases in public health affairs

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Frontiers of Medicine 2012年第2期6卷 173-186页

作者： albert cheung-hoi yu Greg Vatcher Xin yue Yan Dong Mao Hua Li Patrick H.K.Tam Parker Y.L.Tsang April K.Y.Wong Michael H.K.Hui Bin Yang Hao Tang Lok-Ting Lau Neuroscience Research Institute/Department of Neurobiology School of Basic Medical Sciences/Key Laboratory for NeuroscienceMinistry of Education/Key Laboratory for NeuroscienceMinistry of HealthPeking UniversityBeijing 100191China Hai Kang Life Corporation Limited Hong Kong SARChina and Beijing 100176China

Infectious diseases,mostly caused by bacteria and viruses but also a result of fungal and parasitic infection,have been one of the most important public health concerns throughout human *** first step in combating these pathogens is to get a timely and accurate diagnosis at an affordable *** kinds of diagnostics have been developed,such as pathogen culture,biochemical tests and serological tests,to help detect and fight against the causative agents of ***,these diagnostic tests are generally unsatisfactory because they are not particularly sensitive and specific and are unable to deliver speedy *** acid-based diagnostics,detecting pathogens through the identification of their genomic sequences,have shown promise to overcome the above limitations and become more widely adopted in clinical *** we review some of the most popular nucleic acid-based diagnostics and focus on their adaptability and applicability to routine clinical *** also compare and contrast the characteristics of different types of nucleic acid-based diagnostics.

关键词： nucleic acid-based diagnostics infectious disease PCR NASBA LAMP microarray LOAC public health affairs

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Functional study of glutamate-induced nuclear swelling in astrocytes

Functional study of glutamate-induced nuclear swelling in as...

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中国神经科学学会第十二届全国学术会议

作者： Yin Lian Zhang Feng Jiang albert cheung hoi yu Lina Li Laboratory For Functional study of astrocytes Neuroscience Research Institute

The excitatory neurotransmitter glutamate（Glu） is proven to play critical roles in various physiological and pathological processes in the central nervous system（CNS）. Astrocytes are the only cell type responsible for de novo synthesis of Glu in the brain, and serve as the regulator of Glu homeostasis by clearance of Glu from synapses. Under normal conditions, Glu in astrocytes is involved in glutamine synthesis and is metabolized through the TCA cycle. However, the total consumption of Glu in these pathways does not account for the total Glu internalized into astrocytes, indicating a hidden function of intracellular Glu might exist in astrocytes. Here, we observed a specific swelling of astrocyte nuclei in response to extracellular Glu, and identified that the specific localization of Aquaporin 1（AQP1） on the nuclear envelopes of astrocytes was required for such process. Furthermore, gene expression was found to be modulated accompanied with Glu-induced nuclear swelling. Among these genes, 92 genes were upregulated and 211 genes were down-regulated. Some of these genes have been proven to be involved in multiple neuronal activities, especially the regulation of transcription. In addition, translocation of an important transcription factor nuclear factor κB（NF-κB） from cytoplasm to nucleoplasm was also observed. Taken together, these findings might reveal a new function of Glu to mediate neuron-astrocyte communication.

关键词： astrocytes glutamate-induced nuclear swelling AQP1 NF-κB

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Neuroglobin co-localize and migrate with mitochondria in neural cells

Neuroglobin co-localize and migrate with mitochondria in neu...

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中国神经科学学会第十二届全国学术会议

作者： Han Xiao Xu Li Tao Yang Rui Zhao albert cheung hoi yu Lina Li Laboratory For Functional study of astrocytes Neuroscience Research Institute Key Laboratory for Neuroscience of the Ministry of Education

Human brain constitutes 2 % of the total body weight, but utilizes over 20 % of the body oxygen at rest. The discovery of neuroglobin（Ngb） in both neurons and astrocytes suggest that Ngb might be closely involved in brain oxygen homeostasis. In the present study, we have investigated the expression, distribution and mobility of Ngb compared to cytoglobin（Cygb）, a universal cellular respiratory globin, in primary astrocytes and neurons. Unlike Cygb, the expression levels of Ngb in astrocytes and neurons increased under both ischemia and rotenone treatment. A co-localization of either endogenous or recombinant Ngb with mitochondria was evidenced using immunostaining and western blot. Furthermore, the L136 P Ngb mutant enhances the colocalization of Ngb and mitochondria under both normoxic and ischemic conditions. A co-migration of L136 P Ngb with mitochondria in the neurite of neurons was also observed. More interestingly, the co-migration and co-localization of L136 P Ngb with mitochondrial was abolished when cultures were treated with cytoskeleton inhibitors such as cytochalasin D, colchicine and nocodazole. Overall, our data demonstrated that Ngb is a migratory protein in cytoplasm that co-localize with mitochondria under both physiological and pathological conditions. In addition, the co-migration of Ngb with mitochondria requires microfilament. Based on our investigation, we propose the hypothesis that Ngb might have distinctive roles during oxygen transportation in comparison to Cygb and serve as an ‘emergency and mobile’ intrinsic protective protein in nervous system.

关键词： neuroglobin mitochondria astrocytes neurons

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Study of exportin-7 in astrocytes under in vitro ischemia

Study of exportin-7 in astrocytes under in vitro ischemia

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中国神经科学学会第十届全国学术会议

作者： Xi LI Hai-Jie LIANG Rui-Chao CHAI Jiao-Hua JIANG albert cheung hoi yu Neuroscience Research Institute Key Laboratory for Neuroscience(Ministry of Education)Key Laboratory for Neuroscience(National Health and Family Planning Commission)Department of NeurobiologySchool of Basic Medical SciencesHealth Science CenterPeking University Laboratory of Translational Medicine Institute of Systems BiomedicinePeking University

Nucleocytoplasmic transport serves essential functions in maintaining normal physiologic status and responding to abnormal states in eukaryotes,and is dependent on the proper functioning of nuclear transport *** have been 11 importins and 7 exportins identified,but their expression patterns and functions in the brain remain *** this study,we demonstrated that all the importins（***-β,tansportin-1,2,3,and importin-4,5,7,8,9,11,13） and exportins（***-1,2,4,5,6,7 and t） are differentially expressed in cerebral cortex,cerebellum,hippocampus and brain stem,and in primary astrocyte cultures and primary neuron *** these importins and exportins,we confirmed that both the mRNA and protein expression of exportin-7 in cultured astrocytes increased after in vitro *** also achieved consistent results via immunofluorescence method,showing that more exportin-7 accumulated inside the nucleus and around nuclear envelopes,indicating exportin-7 underwent active nuclear shuffling during *** elucidate the potential function of exportin-7,we focused on an exportin-7 target substrate LKB1- a necessary element in cell metabolism that is required for maintaining energy ***,we found that stable mRNA expression of LKB1 but its protein level was up-regulated in astrocytes under in vitro *** also observed the translocation of LKB1 from the nucleus into the cytoplasm under ***,the viability of astrocytes under ischemia improved when transfected with an *** together,these results implied the protective role of exportin-7 in astrocytes against *** function might involve translocation of certain substrates（***1） that are beneficial for survival under metabolic stress.

关键词： Exportin-7 ischemia astrocytes nuclear transport LKB1

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Macropinocytosis speeds up cell migration

Macropinocytosis speeds up cell migration

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中国神经科学学会第十二届全国学术会议

作者： Xu Bo Duan Lu Ye Qin Kai Gao Jiang Shan Zhan albert cheung hoi yu Lina Li Laboratory For Functional study of astrocytes Neuroscience Research Institute Key Laboratory for Neuroscience of the Ministry of Education

Cell migration is a determinant factor in processes such as tumor metastasis, immune response and wound healing. It shares a range of molecular components with endocytosis such as proteins, and also requires cytoskeleton to be involved as in endocytosis. Up to now, there is not enough information to elucidate the underlying mechanisms how actin structures act synergistically with these components in such processes. Here we report that macropinocytosis, a form of cell drinking, can be induced by physical injury and occurs at the site of ruffling membrane in astrocytes which eventually leads an extra rate of cell migration. The unraveled mechanism was a complex multiple signaling pathway, including calcium, PI3 K, Raf-1, JNK and p38, all of which could modulate macropinocytosis in astrocytes. In addition, for the first time, Raf-1 was determined to be a direct regulator of macropinocytosis via the binding with *** interestingly, such mechanism was also evidenced in other type of cells. We propose here a general mechanism that macropinocytosis is an important cellular response to injury;cell migration could be modified through controlling the occurrence of macropinocytosis under physical injury. A novel and important therapeutic target for modulating cell migration related processes such as wound healing and metastasis might be provided.

关键词： cell migration macropinocytosis injury multiple signaling pathway

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DREAM in astrocyte regulates prodynorphin-dynorphin expression and may take part in chronic pain

DREAM in astrocyte regulates prodynorphin-dynorphin expressi...

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中国神经科学学会第十届全国学术会议

作者： Jiao-Hua JIANG Ann yuen Kwan WONG Jun-Hui WANG Feng-Bo SUN albert cheung hoi yu Neuroscience Research Institute Key Laboratory for Neuroscience(Ministry of Education)Key Laboratory for Neuroscience(National Health and Family Planning Commission)Department of NeurobiologySchool of Basic Medical SciencesHealth Science CenterPeking University Laboratory of Translational Medicine Institute of Systems BiomedicinePeking University

Chronic pain,one of the most ancient and costly health problems,is poorly controlled and its underlying mechanisms are not well *** now,increasing evidence indicates that astrocytes may play an important role in the development and maintenance of chronic pain,but the cellular mechanisms involved remains *** neurons,the key pain modulator prodynorphin and dynorphin are known to be involved in chronic pain and are regulated by the Downstream Regulatory Element Antagonist Modulator(DREAM),which is a multifunctional Cabinding *** were generally believed to have no prodynorphin ***,we identified a novel signal pathway of pain cascades in astrocytes:DREAM-prodynorphin-dynorphin,which are three key factors involved in pain ***,as a transcriptional repressor,exhibited nuclear and cytoplasmic distribution and two different polymeric forms in *** with K and exposure to glutamate resulted in down-regulation of DREAM in astrocyte via N-methyl-D-aspartate(NMDA) receptor and PI-3 kinase,followed by the up-regulation of prodynorphin mRNA and dynorphin protein ***,DREAM in astrocytes exhibited different structural properties and cellular locahzation compared to that in glutamatergic and GABAergic *** differential characteristics implicated different roles of DREAM in regulating prodynorphin expression in neurons and *** data suggests that astrocytes may present prodynorphin-dynorphin-related functions and may have the potential in regulating chronic pain through different mechanisms than neurons via the DREAM-prodynorphin-dynorphin pathway.

关键词： astrocytes DREAM prodynorphin dynorphin pain

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AQP1 is involved in glutamate induced nuclear swelling in astrocytes

AQP1 is involved in glutamate induced nuclear swelling in as...

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中国神经科学学会第十届全国学术会议

作者： Feng JIANG Rui Chao CHAI Ann yuen Kwan WONG Chun Zhang YANG Ye ZHOU albert cheung hoi yu Neuroscience Research Institute Key Laboratory for Neuroscience(Ministry of Education)Key Laboratory for Neuroscience(National Health and Family Planning Commission)Department of NeurobiologySchool of Basic Medical SciencesHealth Science CenterPeking University Laboratory of Translational Medicine Institute of Systems BiomedicinePeking University

Glutamate(Glu),the most important excitatory neurotransmitter in the central nervous systems(CNS),mediates synaptic plasticity,learning and *** astrocytes being the absorption sink of excess Glu,the intracellular metabolism of Glu is not fully *** performed H-Glu and immunostaining experiments and demonstrated that internalized glutamate in astrocytes could enter the nuclei,and directly trigger nuclear swelling and gene *** swelling was found to require aquaporin 1(AQP1),a water channel protein expressed in the cytoplasm and cell membrane of many cell types where they play important physiological *** this study,AQP1 was detected specifically on astrocytic nuclear envelop both in vivo and in ***-expression of AQP1 in astrocytes enhanced Glu-induced nuclear swelling,while its inhibition or knock-down by shRNA prevented Glu-induced nuclear *** specialization we found might uncover more potential function of Glu in astrocytes that involves AQPl localization on astrocytes nuclear membrane.

关键词： aquaporin 1 glutamate astrocyte nuclear swelling

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AQP5 is differentially regulated in astrocytes during metabolic and traumatic injuries

AQP5 is differentially regulated in astrocytes during metabo...

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中国神经科学学会第十届全国学术会议

作者： Rui Chao CHAI Jiao Hua JIANG Ann yuen Kwan WONG Feng JIANG Kai GAO Greg VATCHER albert cheung hoi yu Neuroscience Research Institute Key Laboratory for Neuroscience(Ministry of Education)Key Laboratory for Neuroscience(National Health and Family Planning Commission)Department of NeurobiologySchool of Basic Medical SciencesHealth Science CenterPeking University Laboratory of Translational Medicine Institute of Systems BiomedicinePeking University

Water movement plays vital roles in both physiological and pathological conditions in the *** are responsible for regulating this water movement,and are the major contributors to brain edema in pathological ***（AQPs） in astrocytes play critical roles in the regulation of water movement in the ***1,3,4,5,8 and 9 have been reported in the *** with AQP1,4 and 9,AQP3,5 and 8 are less *** the lesser known AQPs,AQP5,which has multiple functions identified outside the central nervous system,is also indicated to be involved in hypoxia injury in *** our study,AQP5 expression could be detected both in primary cultures of astrocytes and ***5 was localized on the cytoplasmic membrane and in the cytoplasm of ***5 expression was down-regulated during ischemia treatment and up-regulated after scratch-wound injury,which was also confirmed in a MCAO model and a stab-wound injury model in *** AQP5 increased after scratch injury was polarized to the migrating processes and cytoplasmic membrane of astrocytes in the leading edge of the scratch-wound,and AQP5 over-expression facilitated astrocyte process elongation after scratch *** together,mese results indicate that AQP5 might be an important water channel in astrocytes that is differentially expressed during various brain injuries.

关键词： aquaporin ischemia MCAO scratch-wound stab-wound

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Upregulation of 14-3-3γ is induced by a synergistic effect of multiple factors during ischemia in astrocytes

Upregulation of 14-3-3γ is induced by a synergistic effect ...

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中国神经科学学会第十届全国学术会议

作者： Ymg PANG Yan DONG Hua-Dong LIU Ann yuen Kwan WONG Greg VATCHER Xiao-Qian CHEN Jian-Guo CHEN albert cheung hoi yu Neuroscience Research Institute Department of Neurobiology Key Laboratory for Neuroscience (Peking University) Ministry of Education Key Laboratory for Neuroscience (Peking University) Ministry of Public Health Department of Neurobiology School of Basic Medical Sciences Peking University Health Science Center Department of Pathophysiology the Key Laboratory of Neurological Diseases the Ministry of Education and Department of Pharmacology Tongji Medical College Huazhong University of Science and Technology Department of Cell Biology and Genetics College of Life Sciences Peking University Key Laboratory for Cell Proliferation and Differentiation Ministry of Education State Key Laboratory for Bio-membrane and Membrane Bio-engineering Laboratory ofTranslattonal Medicine Institute of Systems Biomedicine Peking University

14-3-3γ is a multifunctional acidic protein that is induced by ischemia in neural cells,including astrocytes,and has a neuroprotective *** ischemia,a lack of oxygen（hypoxia） and glucose,and an accumulation of toxins,*** order to elucidate which ischemia components caused the damage to astrocytes and the induction of the protective protein 14-3-3γ,we examined the effects of hypoxia,glucose deprivation,and the accumulation of toxins,separately,and compared the degree of damage to ischemia *** caused a rapid upregulation of 14-3-3γthat occurred within 1 to 4 *** alone elevated 14-3-3γ expression,while glucose deprivation did not cause a detectable change in the 14-3-3γ mRNA and protein *** changes of toxic metabolites barely affected14-3-3γ gene and protein expression in the time course *** addition,comparing the activation of the ERK1/2,Akt,P38 and JNK signaling pathways under ischemia and hypoxia in astrocytes revealed mat ischemia activated all four pathways,while hypoxia had little effect on any of *** also observed how glutamate（Glu） and arachidonic acid（AA）,the main toxic substances released by neural cells during ischemia injury,affected the expression of the14-3-3 protein *** all members of the 14-3-3 family,β and γ were up-regulated rapidly after 3 hr of treatment with G1u or AA,while η and ε increased until 6 hr and ζ increased after *** results demonstrated that the three components of ischemia played diverse roles in the regulation of 14-3-3Y) that different isoforms of the 14-3-3family showed disparate responses to Glu and AA treatments,and that the JNK/c-Jun/AP-1 signaling pathway was involved in 14-3-3γ up-regulation.

关键词： 14-3-3γ hypoxia ischemia glutamate arachidonic acid

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