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Mithramycin A protects neurons from apoptosis via transcriptional inhibition of two BH3-onIy proteins:Bim and Dp5/Hrk

Mithramycin A protects neurons from apoptosis via transcript...

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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： Qiao-Ying HUANG~(1,2),Bo XIE~(1,2),Ming-Tao LI~(1,2,*) 1 Department of Pharmacology,2 Proteomics Center Zhongshan School of Medicine,Sun Yat-sen University,74 Zhongshan RoadⅡ,Guangzhou 510080,China

Mithramycin A,a clinically approved antitumor antibiotic,has been demonstrated to have neuroprotective effects in many different paradigms of neuronal ***,the neuroprotective mechanism of mithramycin A remains to be *** we found that,in the activity deprivation-induced apoptosis of cerebellar granule neurons,mithramycin A protected neurons from apoptosis and inhibited the transcriptional increases of 2 proapoptotic BH3-only proteins Bcl-2 interacting mediator of cell death(Bim) and death protein 5/harakiri(Dp5/Hrk).Either of them has been reported to play a critical role in neuronal apoptosis by us and *** A reversed the dramatic increases of promoter activity and mRNA level of both Bim and Dp5 in a dose-dependent *** also blocked the induction of Bim protein in neuronal apoptosis,despite the fact that we failed to detect endogenous Dp5 ***,mithramycin A had no effect on neuronal apoptosis triggered by overexpression of either Bim or Dp5 *** findings suggest that mithramycin A may exert its neuroprotective effect through inhibiting the transcriptional expression of Bim and Dp5,further supporting mithramycin A as a promising drug for neuroprotection.

关键词： neuroprotection mithramycin A Bim Dp5 cerebellar granule neurons

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A novel method to label the cerebrospinal fluid-contacting neurons in rats

A novel method to label the cerebrospinal fluid-contacting n...

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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： Jia-You WANG~#,Fang ZHOU~#,Li-Cai ZHANG~* Jiangsu Province Key Laboratory of Anesthesiology,Xuzhou Medical College,Xuzhou 221002,China

Objective The study aimed to explore a specific marker to label cerebrospinal fluid-contacting neurons (CSF-CNs)in rat and provide a new way to identify *** Adult Sprague-Dawley rats,male,were randomly received 4 different treatment(n=6):*** toxin subunit B(CB)injection into the cerebrospinal fluidcontacting nucleus(CSF-CN);*** injection into the hippocampus(non-CSF-CN)as control;*** injection into the lateral ventricle;*** labeling method(lateral ventricle injection of CB-conjugated horseradish peroxidase (CB-HRP))as a positive *** received same volume of CB or CB-HRP(1μL).Animals were perfused after 48 h survival and the relevant brain tissue was sectioned(40μm)for immunofluorescence to observe the effects of different labeling *** Group A:Neurons labeled by CB clustered only in the CSF-CN,not in other areas;Group B:In the hippocampus(non-CSF-CN area),there were few CB positive neurons;Group C:CB positive neurons clustered in the CSF-CN;D Group:Neurons labeled by CB-HRP appeared only in the *** is,the method of CB injected into lateral ventricle has the same effects on labeling area with CB-HRP;the method of CB injected into CSF-CN has the same effects with C/D group;the method of CB injected into non-CSF-CN showed that neither CSF-CNs nor non-CSF-CNs was *** Parenchyma injection of CB is a scientific and reliable method to label CSF-CNs in rats.

关键词： CSF-CNs specific label CB

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MicroRNA expression profiling in the hippocampus of rats with depressive-like behavior induced by chronic stress

MicroRNA expression profiling in the hippocampus of rats wit...

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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： Shen-Jun WANG,Lin LU~* Department of Neuropharmacology,National Institute on Drug Dependence,Peking University,Beijing 100083,China

Objective MicroRNAs(miRNAs) are a large family of small non-coding RNAs which negatively control gene expression at both the mRNA and protein *** number of miRNAs identified is growing rapidly and approximately one-third is expressed in the brain where they have been shown to affect neuronal differentiation, synaptosomal complex localization and synapse *** has been proposed that miRNAs may have important roles in complex psychiatric *** and behavioral data have posited miR-16 as a central effector that regulates SERT expression and mediates the adaptive response of serotonergic and noradrenergic neurons to antidepressants *** now,little has been known about the potential involvement of hippocampal miRNAs in *** Male Sprague-Dawley rats were subjected to a sequence of 12 different stressors(two per day) for 35 *** preference test was used to assess rats depressive-like *** expression profiling was identified by using Solexa *** of predicted effectors of candidate miRNAs were generated using the TargetScan program(http://***).Results(1) One miRNA(miR-1224) showed a significant variation with fold change higher than 2.0 and four miRNAs showed decrease(miR-1249,182,183,204).(2) Brainderived neurotrophic factor(BDNF) and CLOCK gene,which have been reported an association with depression,are two predicted miR-182 target *** miR-182 maybe an important molecular regulator that control the complex actions of chronic stress in hippocampus and the neuroadaptations associated with depression.

关键词： microRNA hippocampus depression chronic unpredictable stress

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Expression of Nurrl in rat brain and spinal cord development

Expression of Nurrl in rat brain and spinal cord development

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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： Weibo SHI,Bin CONG,Qian QI,Zuo MIN,Yingmin LI~* Institute of Basic Medicine,Hebei Medical University,Shijiazhuang 050017,China

Nurr1 is a member of the nuclear receptor superfamily and is a regulatory factor of differentiation, migration,and maturation of mesencephalic dopaminergic *** present study was designed to observe the dynamic changes of protein expression of Nurr1 as well as its relationship with proliferating cell nuclear antigen (PCNA) in the rat brain and spinal cord development,and to investigate the significance of Nurr1 in differentiation and migration of nerve ***-embedded sections,immunohistochemistry,immunohistochemical double staining and western blot were *** results demonstrated that in embryo development,the Nurr1-positive cells increased apparently and migrated gradually far from the lateral *** postnatal rats,the positive cells surrounding the lateral ventricle decreased *** expression of Nurr1 in the cerebral cortex peaked at days P1-P5,decreased obviously along with maturation of the cells and became rare in matured cerebral *** staircase-shaped migration from dorsal areas to ventral areas of spinal cord was ***,the positive cells in spinal cord decreased apparently,and there were no positive cells in matured spinal *** comparative observation of Nurr1 and PCNA showed that the two proteins were expressed at different regions and in different cells. Nurr1 was confined to differentiated and migrating immature cells,but not to proliferating *** suggested that Nurr1 might play a regulatory role in the differentiation,migration and maturation of the nerve cells in the rat brain and spinal cord.

关键词： Nurrl differentiation migration PCNA proliferation

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Rolipram inhibits the heroin-seeking behavior induced by heroin priming or heroin-associated conditioned cues in rats

Rolipram inhibits the heroin-seeking behavior induced by her...

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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： Miao-Jun LAI~1,Hua-Qiang ZHU~1,Dan FU~1,Wei-Sheng CHENG~1,Han-Ting ZHANG~(2,*),Wen-Hua ZHOU~(1,*) 1 Laboratory of Behavioral Neuroscience,Ningbo Addiction Research and Treatment Center,School of Medicine, Ningbo University,China 2 Departments of Behavioral Medicine & Psychiatry and Physiology & Pharmacology,West Virginia University Health Sciences Center,USA

Objective Several lines of evidence have suggested a critical role for CREB activities,which activated by changes of cAMP in mediating the rewarding and reinforcement effects of many drugs of *** of phosphodiesterase(PDE) increase the concentration of cAMP and activate the ***,a cAMP-selective phosphodiesterase 4(PDE4) inhibitor has been thought to enhance the cognitive function,but whether the rolipram inhibit the drug seeking behavior is still *** Our aim was to investigate the effect of rolipram,on cueor heroin-primed heroin-seeking in *** were self-administered heroin for 12 days and extinguished for 12 days, then,conditioned cues or heroin priming(250μg/kg) was introduced for the reinstatement of heroin-seeking behaviors. Results The reinstatement of heroin seeking induced by cues or heroin priming was attenuated by administration of rolipram(0,0.3,1 or 3 mg/kg,i.p.) in a dose-dependent *** pretreatment with rolipram did not inhibit the heroin *** expression of p-CREB in nucleus accumbens was increased when pretreatment with *** The data suggested that rolipram could be used as a potential pharmacotherapeutic agent to reduce drug-seeking.

关键词： cognitive enhancer addiction heroin cAMP

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Promoting adult hippocampal neurogenesis:a novel strategy for antidepressant drug screening

Promoting adult hippocampal neurogenesis:a novel strategy fo...

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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： Hua-Cheng YAN~(1,3),Xiong CAO~1,Tian-Ming GAO~1,Xin-Hong ZHU~(1,2,*) 1 Department of Neurobiology,2 School of Traditional Chinese Medicine,Southern Medical University,Guangzhou 510515,China 3 Department of Pharmacy,Guangzhou General Hospital of Guangzhou Military Command,Guangzhou 510010,China

Major depression is a common mood disorder which jeopardizes our health;hitherto almost all of available antidepressants(ADs) have the same core mechanisms of action in promoting serotonin or noradrenaline function in the *** major limitation of today's ADs is that chronic treatment(3-6 weeks) is required before a therapeutic response is *** effective and faster treatments for depression are in urgent *** neurogenesis (the birth of new neurons) continues postnatal and into adulthood in the brains of multiple species,including humans. Recently numerous findings give rise to the hypothesis that AD effect and increasing adult hippocampal neurogenesis may be causally *** classes of ADs increased hippocampal neurogenesis in a chronic but not acute time course,which corresponds to the therapeutic time lag caused by current ADs;whereas ADs would lose their effects in behavioral models of depression when hippocampal neurogenesis was *** review presents the major current approaches to understand adult neurogenesis and the causally connected evidences between AD effects and adult hippocampal neurogenesis,and the potential underlying ***,we will combine with our recent research progresses,which provide a promising strategy that enhancing adult hippocampal neurogenesis might be a new avenue for the development of novelty ADs.

关键词： adult neurogenesis antidepressants dentate gyrus drug screening hippocampus mechanism

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Expression of bone morphogenetic protein-4 in cortical lesions of focal cortical dysplasiaⅡb and cortical tubers of TSC

Expression of bone morphogenetic protein-4 in cortical lesio...

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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 GUO,Chun-Qing ZHANG,Si-Xun YU,Hai-Feng SHU,Bang-Yun ZHAO,Hui YANG~* Department of Neurosurgery,Xinqiao Hospital,Third Military Medical University,Chongqing,China

Objective Malformations of cortical development(MCDs) represent a well-recognized cause of intractable *** morphogenetic proteins(BMPs) are members of the transforming growth factor(TGF) superfamily of *** aim of this study is to define the expression and the cellular distribution of BMP- 4 in focal cortical dysplasia(FCD) typeⅡb and tuberous sclerosis complex(TSC).Methods We have studied surgically resected tissues from 19 patients,12 FCDⅡb and 7 ***-appearing control cortex/white matter was obtained at autopsy from 5 patients without a history of seizures or other neurologic *** blot and immunocytochemistry were *** Western blot analysis showed that there was a statistically significant decrease of BMP-4 protein level both in MCD comparison with ***-staining results showed that moderately-strongly staining was widely observed in neurons and glial cells in *** dysplasia cortex of FCDⅡb,BMP-4 was widely expressed in normal-appearing neurons and reactive astrocytes,more intensely expressed in giant neurons(GNs),dysplastic neurons(DNs) and balloon cells(BCs).In cortical tubers,it showed similar features with FCDⅡ*** The reduced expression and specific cellular distribution of BMP-4 suggested a possible contribution of BMP-4 to the dysplasia cortex of these malformations of cortical development.

关键词： bone morphogenetic protein focal cortical dysplasia tuberous sclerosis complex epilepsy

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Fibroblast growth factor 7 acts as a modulator of nociception

Fibroblast growth factor 7 acts as a modulator of nociceptio...

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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： Hui LIU~1,Qing-Feng WU~1,Qiong WANG~2,Lan BAO~2,Xu ZHANG~1 1 Institute of Neuroscience and State Key Laboratory of Neuroscience,2 Institute of Biochemistry and Cell Biology and Laboratory of Molecular Cell Biology,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences, Shanghai 200031,China

Fibroblast growth factor(FGF)7,which is also known as keratinocyte growth factor(KGF),is a member of the FGF *** studies regard it as a locally acting epithelial mitogen that is produced by cells of mesenchymal origin and has an important role in protecting and repairing epithelial ***,its potential functions in the nervous system are poorly *** found that FGF7,together with its high-affinity receptor FGFR2b,was expressed in both dorsal root ganglion(DRG)and spinal cord ***7 mRNA was consistently increased in DRGs after peripheral nerve injury and transiently up-regulated after intraplantar injection of complete Freund's *** injection of recombinant human FGF7 exacerbated the formalin-induced hyperalgesia, while application with either the antibodies against FGF7 or recombinant FGF R2β(Ⅲb)Fc chimera alleviated inflammatory nociceptive ***,behavior tests and wide-dynamic range neuron recordings of FGF7 knockout mice showed a defect in nociceptive *** together,these results suggest that FGF7 may contribute to inflammatory pain sensation and play an important role in nociceptive transmission.

关键词： fibroblast growth factor 7 inflammatory pain nociceptive transmission

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EGF enhances the migration of cancer cells by up-regulation of TRPM7

EGF enhances the migration of cancer cells by up-regulation ...

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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-Xia GAO,Hai-Lin ZHANG Department of Pharmacology,Hebei Medical University,Shijiazhuang 050017,China

Ion channels are involved in the migration of tumor cells that is required for their invasion and metastasis. In this present study,we describe the role of TRPM7 channel plays in the migration of A549 lung cancer *** TRPM7 currents in A549 cells were first characterized by using means of electrophysiology,pharmacology and RNA interference,and the expression of TRPM7 in A549 cells were also confirmed in mRNA and protein levels. TRPM7 currents in A549 cells have characteristics similar to that of TRPM7 currents reported,with strong outward rectification and sensitive to the inhibition of internal and external divalent *** growth factor(EGF),an important player in cancer development,greatly enhanced the migration of A549 cells and at the same time markedly up-regulated the expression of TRPM7 protein and the current amplitude of *** of TRPM7 function with RNA interference or pharmacological agents no only reversed the EGF-enhanced migration of A549 cells but also inhibited the basal migration of A549 cells in the absence of added ***,the EGF-induced reorganization of cytoskeleton of A549 cells was also prevented by blocking of TRPM7 *** it seems that TRPM7 plays a pivotal role in the migration of A549 cells and TRPM7 could be a potential therapeutic target in lung cancers.

关键词： TRPM7 EGF lung cancer migration

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Sodium salicylate,an aspirin metabolite,lowers the excitability of the medial geniculate body

Sodium salicylate,an aspirin metabolite,lowers the excitabil...

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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： Yan-Yan SU~1,Bin LUO~(1,*),Lin CHEN~(1,2,*) 1 Auditory Research Laboratory,School of Life Sciences,University of Science and Technology of China,Hefei 230027, China 2 CAS Key Laboratory of Brain Function and Disease,University of Science and Technology of China,Hefei 230027,China

Previous studies suggest that sodium salicylate(NaSal),an asparin metabolite,raises the neural excitability in the auditory cortex to cause *** the present study,we wanted to determine whether NaSal had a similar effect in the medial geniculate body(MGB),a central auditory structure that provides the immediate inputs to the auditory *** whole-cell patch-clamp recordings from MGB slices in rats,we measured effects of NaSal(1.4 mmol/L) on neuronal intrinsic properties and the synaptic *** found that NaSa1 decreased the membrane input resistance,hyperpolarized the resting membrane potential,suppressed the current-evoked firing,changed action potential properties and depressed rebound *** also reduced the postsynaptic response evoked by stimulating the brachium of inferior colliculus(BIC),indicating a reduction in efficacy of the synaptic transmission. Our results demonstrate that NaSal lowers the neural excitability via altering neuronal intrinsic properties and reducing the synaptic transmission in the MGB,which is distinct from its excitatory effects on the auditory *** suggest that NaSal-induced tinnitus may be partly due to the abnormal neural synchrony in the auditory cortex resulting from the reduced excitability of the MGB.

关键词： brain slice intrinsic property medial geniculate body salicylate synaptic transmission tinnitus whole-cell patch-clamp

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