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Inhibition of autophagy aggratated oxygen-glucose deprivation/reperfusion induced neuron injury in vitro

Inhibition of autophagy aggratated oxygen-glucose deprivatio...

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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： Xiang-Nan ZHANG,Hai-Jing YAN,Yan-Ying FAN,Wei-Wei HU,Zhong CHEN~* Department of Pharmacology Key Laboratory of Medir.al Neurobiology of Ministry of Health of China Zhejiang Province Key Laboratory of Neurobiology School of Basic Medical Sciences College of Pharmaceutical Sciences, Zhejiang University,Hangzhou 310058,China

Objective Several lines of evidences indicated that autophagy was involved in ischemic brain injury. Ischemia/reperfusion injury may lead to autophagic cell death,while some studies also suggested that autophagy can be beneficial by eliminating damaged organelles and mis-folded ***,it is necessary to determine whether autophagy is protective or detrimental in ischemia/reperfusion（OGD/Rep.） *** To deal with this issue,the primary cultured rat cortex neurons were carried *** 7 days culture in vitro,the culture medium was replaced by glucose-free DMEM and neurons were subjected to a sealed chamber completely infused with oxygen-free gas（95%N+5%CO）.After incubation in 37℃for 2 h,reperfusion was performed by the presence of glucose（4.5 g/L） and oxygen（5%CO+air） in 37℃for 24 *** were treated with 3-methyladenosine（3-MA） and bafilomycin A1（Baf A1）,two well accepted autophagy inhibitors,when reperfusion *** viability was deteced by methyl thiazolyl tetrazolium（MTT） *** OGD/*** cell viability to（67.4±1.6）%of control group（P<0.01）.Treatment with both 3-MA and Baf A1 further decreased cell viability in a concentration-dependent manner（P<0.05 vs OGD/***）,suggesting a protective role of autophagy in our *** addtion,treatement with 3-MA or Baf Al in the first 4 h-period of reperfusion aggratated neuronal cell injury as well,but not in the first 2 h- or the second 4 h-period of *** results suggested that there may be a time-window for autophagy regulation in OGD/Rep.-induced neuron *** Autophagy may play a protective role in OGD/*** neuron cell *** in reperfusion phase could be a novel target for cerebral ischemia therapy.

关键词： autophagy cerebral ischemia oxygen-glucose deprivation neuroprotection

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[Gly14]-humanin abolished Aβ31-35-induced neurotoxicity by activating STAT3 transcription factor pathway

[Gly14]-humanin abolished Aβ31-35-induced neurotoxicity 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： Li YUAN,Xiao-Jie LIU,Zhao-Jun WANG,Wei-Na HAN,Wei YANG,Jin-Shun QI~* Department of Physiology,Shanxi Medical University,Taiyuan 030001,China

Objective Humanin（HN）is a 24-amino acid bioactive peptide abolishing neuronal cell death induced by various familial AD-related genes and amyloid-p（Aβ）.[Gly]-humanin（HNG）,a derivative of HN,has been reported to have much stronger neuroprotective effects than natural HN in vitro and in *** previous studies also indicated that HNG could protect against Aβ-induced impairments of hippocampal LTP and spatial learning and ***,the underlying molecular mechanisms by which HNG plays neuroprotective roles remain largely *** view of the important roles of STATs and Caspase-3 in normal cellular activities or pathological apoptosis,the present study is designed to explore the influence of HNG on the gene expression of STAT3 and Caspase-3 in the AD related animal *** SD rats were pretreated by intrahippocampal injection of Aβ31- 35,HNG,and genistein（a specific inhibitor of tyrosine kinases）.The expressions of STAT3 and Caspase-3 mRNA in the hippocampus were analyzed in real-time ***（1）Compared with control,the level of Caspase-3 mRNA,in 5 nmol Aβ31-35 alone group,significantly increased,while STAT3 mRNA expression showed an obvious decrease.（2）2 nmol HNG alone injection up-regulated STAT3 mRNA and down-regulated Caspase-3 mRNA.（3）In co-injection of HNG plus Aβ31-35 group,the expression of Caspase-3 mRNA was markedly reduced and the level of STAT3 mRNA was increased compared with Aβ31-35 alone group.（4）After pretreatment with Genistein,the neuroprotective effect of HNG was significantly reduced in co-application of Genistein,HNG and Aβ31-35 group. Conclusion（1）The Aβ-induced impairments of hippocmpal synaptic plasticity and animal cognitive behavior may be involved in the activation of Caspase-3-dependent intrinsic apoptotic pathways,as well as the suppression of STAT3 mRNA expression.（2）The neuroprotective effects of HNG against Ap neurotoxicity might be mediated by activating tyrosine kinase and STAT3 transcription factor,and blocking

关键词： [Gly14]-humanin amyloid-p protein STAT3 Caspase-3 real-time RT-PCR

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Interactions between vl and v4 in processing global visual contours

Interactions between vl and v4 in processing global visual c...

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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： Charles D.Gilbert Lab.Neurobiol Rockefeller Univ.New YorkNYUSA

Objective Integration of local image components into global shapes is crucial for perceiving coherent objects in visual *** studies indicate that V1 is involved in mediating contour integration—a delayed component of neuronal responses in V1 is predictive of perceptual saliency of *** contour-related responses are subject to the influences of attentional control and perceptual learning,which suggests task-dependent gating of contextual interactions in V1 via feedback connections from higher cortical *** To test this speculation directly,we chronically implanted Utah arrays into retinotopically matched regions in macaque V1 and V4,and trained the animal to detect visual contours formed by collinear bars embedded in a background of randomly oriented bars. Results By comparing neuronal activity recorded simultaneously in these two areas in response to the same contour stimuli in the detection task,we could replicate earlier findings in V1(Li et al.,Neuron 2006,2008)—neuronal responses that were strongly correlated with the length of the global contours did not appear until 100 ms after stimulus onset,about 60 ms longer than the response latencies of V1 neurons to the *** contour activated neuronal responses in V4,however,showed a different time *** the response outset,which was on average about 15 ms later than that in V1,neurons in V4 already carried information about contours of different lengths,although the contour-related responses were weaker than those seen in the late components of both V1 and V4 ***, as the contour-related responses evolved with time in these two cortical areas,contour activated responses reached a maximum strength first in V4,about 15 ms earlier than *** Our observations suggest that V4 detects the presence of a global configuration of contours earlier than V1,and that the countercurrent processing via feedforward and feedback connections between lower and higher cortical

关键词： contour integration primary visual cortex visual area 4 timing feedback gating

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Roles of nuclear receptors LXRs and ERs in the neuroprotection of dopaminergic neurons in the midbrain

Roles of nuclear receptors LXRs and ERs in the neuroprotecti...

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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-Qiong GUO~1,Hong-Liang YI~1,Xiao-Tang FAN~2,Hai-Wei XU~(3,*) 1 Department of Physilogy,Third Military Medical University.Chongqing 400038,China 2 Department of Histology and Embryology,Third Military Medical University,Chongqing 400038,China 3 Southwest Eye Hospital,Southwest Hospital,Third Military Medical University,Chongqing 400038,China

Objective To explore the roles of liver x receptors(LXRs) and estrogen receptors(ERs) in the activation of microglia and astrocyte in the substantia nigra(SN) of the midbrain and its relationship with the degeneration of dopaminergic *** The expression of LXRs subtypes(LXRa and LXRβ) and the ERs subtypes(ERa and ERp) in the midbrain of mice was detected with RT-PCR and ***α-/-,LXRβ-/-,LXRaβ-/- mice,ovariectomy mice and wildtype mice were used in this *** wildtype mice and ovariectomy mice were treated with agonist of LXR TO901317 and 17β-estradiol *** protein levels of ERK and AKt were detected by Western ***(1) Both LXRα,LXRβ,ERa and ERβare expressed in the midbrain of fourmonth old mice,and LXRβis expressed at higher levels than LXRα.Immunohistochemistry confirmed the expression of LXRs and ERs.(2) Compared with age-matched WT mice,microglia and astrocyte were over-activated in LXRβ-/- and LXRαβ-/- mice,of which glia over-activation are more remarkably in the LXRα-/-β-/- *** the number of TH-positive neurons in the SN and TH-ir fiber density in SNpr were decreased in the LXRβ-/-,and extremely reduced in the LXRα-/-β-/- mice.(3) Intraperitoneal injection of LPS to the 4-month-old female WT mice can trigger microglia activation and release inflammatory factors such as IL-1β,IL-6 and TNF-α.LXR agonist TO901317 can effectively block the activation of microglia and reduce mRNA levels of proinflammation factors including IL-1β, IL-6 and TNF-α.(4) The number of TH-IR neurons and the gene expression level of DAT significantly decreased in ovariectomized mice,and treatment with estrogen can prevent the reduction of *** derived neurotrophic factor was involved in the effect of *** By modulating the activation of microglia and astrocyte and their function of pro-inflammatory factors and neurotrophic factors level,both LXRβand ERβproduce neuroprotection effect on dopaminergic neuron

关键词： liver x receptor estrogen receptor dopaminergic neuron microglia astrocyte

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Phosphorylation-dependent regulation of APP by PP2A is involved in Aβproduction

Phosphorylation-dependent regulation of APP by PP2A is invol...

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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： Xin Zhou~1,Gong-Ping LIU~1,Jian-Zhi WANG~* 1 Department of Pathophysiology,Key Laboratory of Neurological Disease of Education Ministry of China,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China

Objective In the amyloidogenic pathway,cleavage of APP by p-secretase generates an N-terminal soluble fragment(sAPP)and beta C-terminal fragment that is sequentially cleaved by y-secretase to produce the Aβpeptides. Threonine 668(T668)in the cytoplasmic domain of APP can be phosphorylated in vivo by a number of protein kinases,including GSK-3P,CDK5,CDC2 and JNK *** of these kinases are associated with neurotoxicity and implicated in neurodegenerative *** may play a key role in regulating the stability of APP,its interaction with intracellular partners and downstream signaling *** has been well recognized that an imbalanced regulation in protein kinases and protein phosphatases is the direct cause for the AD *** doubt that PP2A which considered being involved in the pathogenesis of AD can affect phosphorylation of APP at T668 to regulate Aβ*** N2a cells stable transfected with human APP(N2a-APP)were transiently transfected with GFP-PP2AsiRNA and Dsred-PP2A,Forty-eight hours after transfection,the protein level of phosphor-APP and total APP were determined by *** N2a-APP cells and the hippocampus of SD rats were also administrated with Okadaic acid(OA)or DES(c6-ceramide)by 24 *** Immunoblot was used to detect the level of phosphor-APP and *** Abeta level of cells and animals were detected by ELISA ***(1)Inhibition of PP2A by OA or siRNA can increase the phosphorylation of APP.(2)Activation of PP2A by DES or overexpression seems not affect the level of phosphor-APP.(3)The incretion of phosphor-APP by OA may not only owe to ***1 as an important phosphatases inhibited by OA may play a role in phosphorylation of APP and Abeta secretion.(4)The Aβlevel increased after injection on hippocampus of SD rats with 0.6 uM *** These results indicated that PP2A which considered to be involved in the pathogenesis of AD can affect phosphorylation of APP at T668 to regulate Aβgeneration.

关键词： APP Aβ PP2A T668

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Central sensitization in hypothalamic arcuate nucleus induced by peripheral inflammation

Central sensitization in hypothalamic arcuate nucleus induce...

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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： Jian-Ming PENG,Xiao-Yong LI,Ning-Ang LIU,Wei LI,Long-Sheng XU,Xing-Hong JIANG~* Key Laboratory of Pain Basic Research & Clinical Therapy,Department of Neurobiology and Institute of Neuroscience,Medical College of Soochow University,Suzhou 215123,China

Objective In recent years great progress has been made in the study of central sensitization of nociceptive neurons in the spinal cord,in which the glutamate NMDA receptor plays a pivotal *** less is known about sensitization in the supraspinal centers related to the pain *** aim of this study was to test whether central sensitization can be induced in nociceptive neurons in the hypothalamic arcuate nucleus by peripheral inflammation, which is known to be one supraspinal component of the endogenous pain-modulating *** Peripheral inflammation was induced by plantar injection of complete Freund's adjuvant(CFA)into the hind paw of *** unit neuronal activity was recorded from the arcuate nucleus(ARC)in the slice of mediobasal hypothalamus as well as in anesthetized *** following inflammation was measured by behavioral paw withdrawal responses. The function of NMDA receptor in ARC was detected by Western blot *** receptor antagonists and kinase inhibitors were used to analyze the underlying mechanisms of signal transduction *** Behavioral measurement confirmed a definite hyperalgesia following peripheral *** sensitization was found in ARC as evidenced by(1)significant increase in the frequency of spontaneous unit discharge of ARC neurons from brain slice of inflamed rats,as well as from anesthetized inflamed rats,as compared to the control rats;(2)enhancement of responses of ARC neurons to glutamate and NMDA application in slice of inflamed rats,and the responses of ARC neurons to non-noxious and noxious stimulation in anesthetized inflamed rats were enhanced as ***-regulated expression of phospho-NRl and phospho-NR2B subunit,rather than NR1 and NR2B,was observed in ARC of inflamed ***-ARC microinjection of MK-801(NMDA receptor antagonist),Ro25-6981 (NR2B subunit antagonist),CNQX(non-NMDA receptor antagonist)and PP2(Src protein tyrosine kinase selective inhibitor)cou

关键词： hypothalamic arcuate nucleus central sensitization hyperalgesia NMDA receptor,NR2B subunit Src tyrosine kinase inflammation

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A novel strategy for partial functional recovery of completely transected lower thoracic spinal cord of adult rats

A novel strategy for partial functional recovery of complete...

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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： Ting-Bao ZHAO~(1,2,#),Shi-De LIN~(2,#),Xiao-Jun ZHANG~(1,2,#),Shu-Guang YANG~(1,#),Fan-Wen KONG~(1,#),Zheng YONG~3, Fang-Jin CHEN~1,Zhao-Qing LIU~1,Hai-Ping QUE~1,Guo-Hua WANG~1,Jian-Quan ZHENG~3,Dong-Hua TIAN~(1,4),San-Jun HU~5,Shu-Qian JING~(1,4),Shao-Jun LIU~(1,2,4,*) 1 Department of Neurobiology and State Key Laboratory of Proteomics,Institute of Basic Medical Sciences,27 Taiping Road,Beijing 100850,China 2 Department of Spinal Cord Repair,Jinan General Hospital,25 Shifan Road,Jinan 250031,China 3 Beijing Institute of Pharmacology and Toxicology,27 Taiping Road,Beijing 100850,China 4 School of Social Development and Public Policy,Beijing Normal University,19 Xinjiekou Wai St.Beijing 100875, China 5 Institute of Neuroscience,The Fourth Military Medical University,Xian 710032,China

Completely transected rat lower thoracic spinal cord was bridged either immediately or lingeringly by microsurgically linking T7 intercostal nerves to L3 dorsal root stumps to establish a bridged *** surgical sites were treated locally with a neurotrophin/growth factor *** the surgery,partial hind limb locomotion and visceral function were gradually *** nerve fibers were then traced to pass through linking sites,grow into L3 dorsal root stumps,enter the spinal cord and eventually contact with neurons in the gray matter of the spinal cord between L2 and *** bridged nerves could trigger evoked potentials in sciatic nerve, bladder,and colon,and induce hind limb *** the bridged nerves transected,the evoked potentials and hind limb locomotion disappeared,urinary retention and feces incontinence occurred *** observations demonstrate that physical and functional linkages between the segments of injured spinal cords have been established by bridging *** is first evidence that the peripheral nerves grow into the central nerve *** importantly,this innovative strategy is potentially applicable for clinic.

关键词： spinal cord injury novel strategy functional recovery neurotrophin/growth factor cocktail

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Motor function impairment delays response of stroke patients during mental rotation task

Motor function impairment delays response of stroke patients...

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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： Jing YAN~1,Xiao-Li GUO~(1,*),Jun-Feng SUN~2,Shan-Bao TONG~2 1 Department of Biomedical Engineering,Shanghai Jiao Tong University,Shanghai 200240,China 2 Med-X Research Institute,Shanghai Jiao Tong University,Shanghai 200030,China

Objective Motor impairment is one of the major disabilities in stroke patients.A variety of methods for improving motor functions have been proposed so far,among which,mental practice-based training,*** imagery（MI）,has been promising one and gaining more attention in the rehabilitation of stroke over last decade. MI has been proved effective in stroke recovery when subjects only imagine body actions without true executions. However,MI is difficult to assess as a covert active process in working memory without overt ***, fMRI studies have revealed the involvement of BA4,supplementary motor areas（SMA）,dorsal premotor,primary motor cortex（Ml）,and *** MI,which were considered as the prime targets of post-stroke *** example of MI,mental rotation task（MRT）,has been successfully used in stroke *** this study,we further investigate the different roles of four cognitive sub-stages in MRT（i.e.）.（i） stimulus perceptual encoding（identification of stimuli and its orientation）,（ii） mental rotation itself,（iii） parity judgment,（iv） response selection and execution) in stroke rehabilitation by behavior and electroneurophysiologic *** Fourteen stroke patients and twelve age-matched healthy control subjects participated in this study with written informed *** the MRT experiment,pictures of either left or right hand at different orientations were randomly *** behavior (*** time（RT） and accuracy) and EEG/ERP data were simultaneously recorded respectively by E-Prime 2.0（Psychology Software Tools Inc,Pittsburgh,USA） and Vision Recorder 1.10（Brain Products GmbH,Gilching, Germany） for each *** repeated-measures ANOVA was used for statistical *** The preliminary results show that RT increased with angle and have the maximum at 180°for both control subjects and stroke patients. Although both groups could accomplish MRT successfully,compared with control subjects,the stroke patient

关键词： stroke motor imagery mental rotation task behavior event-related potential(ERP)

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IL-6 elevation in brain causes neural circuitry imbalance and mediates autism-like behavior

IL-6 elevation in brain causes neural circuitry imbalance an...

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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： Kathryn K.Chadman Daniel P.McCloskey Ashfaq M.Sheikh Mazhar Malika W.Ted Brown Department of Neurochemistry NY State Institute for Basic Research in Developmental DisabilitiesNew YorkNY 10314USA Department of Psychology and Center for Developmental Neuroscience College of Staten IslandNew YorkNY 10314USA

Objective Autism is a severe neurodevelopmental disorder characterized by problems in communication, social skills,and repetitive *** immune responses have been suggested to be associated with autism. Cytokines including IL-6,IL-8,IL-12,IL-1β,TNF-α,IFN-7,TGF-β1 and MCP-1 were reported to be increased in the blood,brain,or cerebrospinal fluid of autistic *** IL-6 is the most consistent finding in autism. However,the mechanisms of how IL-6 being involved in the pathogenesis of autism are poorly *** A mouse model of stably over-expressing IL-6 in brain was developed by injecting adenovirus encoding GFP IL-6 fusion protein into the cerebral lateral ventricles of P0.5 mice.A set of behavior tests was carried out to investigate the behavior in IL-6-over-expressed *** expression of synaptic vesicle proteins was tested using the fluorescence *** Dil labeling was used to outline dendritic spines in pyramidal *** synaptic function was measured with extracellular field excitatory post-synaptic potentials recordings in CA1 area of the hippocampus in acute *** We showed for the first time that elevation of IL-6 in the mouse brain produced certain autistic features,including impaired cognitive abilities,deficits in learning,abnormal anxiety-like traits and habituation, as well as decreased social interactions in older *** investigate how IL-6 elevation leads to the development of autistic phenotype,we detected that an IL-6 elevation resulted in increased excitatory synaptic formations and a decreased number of inhibitory ***-6 elevation produced an increase in the length of dendritic spines and also stimulated the formation of mushroom-shaped dendritic *** addition,we demonstrated that IL-6 elevation reduced postexcitatory inhibition in the mouse *** An abnormal elevation of IL-6 in the brain could lead to the development of autism phenotype through its impairments in

关键词： autism IL-6 synapse development synaptic transmission autistic-like behavior

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The morphological development of layer 1 neurons in mouse neocortex

The morphological development of layer 1 neurons in mouse ne...

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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： Xing-Hua YAO,Yong-Chun YU~* Institute of Neurobiology,Fudan University,Shanghai,200032,China

Objective Layer 1 is the top layer of the cerebral cortex,which originates from the neocortical marginal zone(MZ).Although recently studies showed that layer 1 mainly populated Cajal-Retzius(C-R) Cells and some types of interneuron,the developing morphological properties of layer 1 neurons remain incompletely *** 3-D model neurons reconstructed from neurobiotin-labeled neurons in the mouse neocortical layer 1,this study provides a detailed morphological analysis at early postnatal days(P) from P1 to *** quantification provides new insight into the potential value of the layer 1 neuron morphology for cortical information *** We micro-injected 4% neurobiotin into layer 1 neurons from P1 to P15 under the neocortical horizontal *** revealed neurobiotin with Cy3-streptavidin,we reconstructed the neurons and analyzed their morphological ***(1) For the interneuron, three developmental periods were revealed,which were characterized by distinct growing rates and properties of alterations in different *** P1 to P5,the interneurons had a few short dendrites with a low density of *** P6 to 8,the extending of dendritic branches and the densities of spines were significantly increased. After P9,almost all compartments of interneuron grew slow.(2) Typical C-R cells showed an ovoid soma,a thick stem dendrite originating from one pole of the soma and a long main axon originating always from the opposite pole of the *** types of C-R cells according the dendritic branches,bipolar and multi-polar,were observed during P1 to P7. After P8,the number of C-R cells was dramatically decreased.(3) Dye coupling is a frequent observation in the immature *** about 30%of the neurobiotin-labeled C-R cells dye coupling to a group of 2-20 neurons in layer 1 and 2-5 pyramidal neurons in layers 2-3 were observed.(4) At P15,we found two types of intemeuron in layer *** two third of the neurons look like ne

关键词： Layerl neocortex morphological development Cajal-Retzius cell interaeuron

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