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Neurotensin expressed by glioma-initiating cells affects clinical outcome in glioma patients

Neurotensin expressed by glioma-initiating cells affects cli...

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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： Liang YI Hualiang XIAO Minhui XU Tunan CHEN Fei LI Mei LI Chunxia LUO Mingyue ZHAO Hua FENG Department of Neurosurgery Southwest Hospital Third Military Medical University Chongqing China Department of Pathology Daping Hospital Third Military Medical University Chongqing China Department of Neurosurgery Daping Hospital Third Military Medical University Chongqing China

Malignant glioma is the most common and fatal tumor in central nervous system, with the poor prognosis even with the advanced *** new prognostic factors and molecular targets may contribute to the understanding ofmalignance progression and patient ***, we investigated the neurotensin (Nts) expression in a series of 116 patients with gliomas of different histology grades and primary cultured glioma initiating cells (GICs).The correlation between Nts expression and the prognosis was *** effect of Nts expression on GICs proliferation was also *** found that NTS expression was detected in 70.9% of malignant gliomas and was significantly (P =0.015) related with a poor *** analysis indicated that Nts expression (P =0.007) was independent predictors of poor ***, the results revealed that Nts was mainly expressed by GICs, not by differentiated glioma *** of Nts expression resulted in a significant reduction of GICs *** study indicated that the expression of Nts positively correlated with the histology grades ofmalignances and could be identified as a prognostic marker in patients with *** which are highly expressed in GICs promoted the proliferation of GICs in an autocrine fashion and might be a potential target to restrict self-renewal of GICs.

关键词： neurotensin glioma stem cells glioma prognosis marker

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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届会员代表大会

作者： Kong-Yan WU Ai-Li SHENG Wen-Wen LIU An-Qi GENG Xing-Yu JIANG Xiao-Bing YUAN Zhen-Ge LUO Institute of Neuroscience State Key Laboratory of Neuroscience Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200031 China CAS Key Lab for Biological Effects of Nanomaterials and Nanosafety National Center for NanoScience and Technology Beijing 100190 China

Guidance cues are critical for axon navigation and ultimately for the wiring of the neuro-circuits during nervous system *** cones of growing axons can sense both attractive and repulsive cues in the environment and make a corresponding ***3A, a negative guidance cues, can collapse growth cones of outgrowing axons, however, the intracellular molecular mechanisms are not well *** we show that the small GTPase Rab5 is involved in growth one collapse in response to ***5 activity assay shows that Rab5 is transiently activated after treatment with *** cone collapse is abolished by down-regulation of Rab5 by specific siRNA in response to *** advantage of live cell FRET assay, we demonstrate that semaphorin3A can activate Rab5 and promote the retrograde trafficking of Rab5 positive endosomes in growth ***5 is required for endocytosis of the growth cone plasma membrane during growth cone collapse.

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

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The regulation of carotid body in the process of anti-hypoxia injury on the CHL1-null mice

The regulation of carotid body in the process of anti-hypoxi...

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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： Jia SUN Xin HUANG Ling-Ling ZHU Ming FAN Institute of Basic Medical Sciences Academy of Military Medical Sciences Beijing 100850 China

Objective Close homolog of L1 (also known as neural cell adhesion molecule L1-like protein, CHL1) is a cell adhesion molecule which plays an important role in organism repair of *** recent years there has been evidence of the relation between CHL1 and nervous system *** the role of CHL1 protein in hypoxia injury has not been *** present study is to explore the impact of CHL 1 deficiency on the tolerance of mice to acute hypoxia and the Phenotype and Protein Expression of Mouse Carotid *** The hypoxia toleration of CHL1+/+ and CHL1-/-mice was evaluated by survival time in a normobaric hypoxia *** blot assays were used for measurement of protein expression in carotid *** and Immunofluorescence staining were used for showing morphological structure of carotid *** (1) CHL1 gene deletion increases tolerance to acute hypoxia in the mouse.(2) The total volume, number of TH+ cells and TH protein expression are increased in CHL1-/-carotid *** CHL1 gene deficiency of mice could change the morphology and function of carotid body, which could explain the enhanced tolerance of CHL1-/-mice to hypoxia.

关键词： CHL 1 carotid body hypoxia

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Slowed vesicle priming and enhanced synaptic depression at syntaxin-1B deficient calyceal synapses

Slowed vesicle priming and enhanced synaptic depression at s...

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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： Jian-Li GUO Xue-Feng WANG Hao TIAN Jian-Yuan SUN Institute of Biophysics Chinese Academy of Sciences State Key Laboratory of Brain and Cognitive Science Beijing 100101 China

Syntaxin 1(STX1), including STX1A and STX1B, is a SNARE protein located at presynaptic membrane and considered to be critical for synaptic vesicle priming and ***, the previous studies have shown that homozygous STX 1A KO mice exhibited no significant phenotype in both synaptic vesicle release and animal *** determine whether/how STX1B functions in vesicle priming and release kinetics, a STX 1B hypomorph mouse line (XT1B) was ***-cell patch clamp recordings from these STX1B mutant Calyx of Held synapses showed fewer spontaneous EPSC (mEPSC) and widened action potential-evoked EPSC (eEPSC).Under train stimulations, STX 1B mutation caused reduction of the eEPSC amplitude at steady state and the enhancement of synaptic ***, STX1B deficiency largely slowed the recovery of RRP after depletion, suggesting the impairment of vesicle *** summary, this study shows that syntaxin 1B protein, as a critical determinant of vesicle release efficiency, modulates releasable vesicle priming and vesicle exocytosis.

关键词： Syntaxin 1B exocytosis priming synapse short term plasticity

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The neurotoxicity mediated by astrocytes involved in fragile X syndrome

The neurotoxicity mediated by astrocytes involved in fragile...

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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： Qi YANG Kun ZHANG Bin FENG Yan-Yan GUO Zhao-Hui XU Jie HAN Lan MA Yu-Mei WU Ming-Gao ZHAO Department of Pharmacology School of Pharmacy Fourth Military Medical University Xi''an 710032 China

Fragile X syndrome (FXS) is a common inherited mental retardation caused by the lack of fragile X mental retardation protein (FMRP) due to silencing of the FMR1 *** studies suggest glia play an important role in the progression of some neurodevelopmental disorders, which including *** we found that knockout astrocytes from a fragile X mouse cannot support the normal dendritic morphology in the coculture *** their conditioned medium, we confirmed Fmrl KO astrocytes caused the abnormal neuronal growth via the neurotoxic ***, we found that Neurotrophin-3 (NT-3) and glutamate were both elevated released in KO astrocytic conditioned medium (ACM).Moreover, we identified that (1) excessive NT-3 was attributed to the oxidative stress in FXS, (2) increased glutamate synthesis and release was resulted from higher expression of glutaminase and vesicular glutamate transporter2 (VGLUT2) in Fmrl KO astrocytes, (3) overeproduction of NT-3 and glutamate in WT ACM can mimic the abnormal neuronal morphology in KO *** results support that astrocytes contribute to the dysregulated neurodevelopment of FXS and astrocytic NT-3 or glutamate production could be a therapeutic target for FXS.

关键词： Fragile X syndrome astrocytes neurotrophin-3 glutamate neurotoxicity

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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 α-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届会员代表大会

作者： Minjuan BIAN Fengyan SUN Fang HUANG Jie LIU Xiaoqi HONG Yufang HUANG Mei YU Yanlong HONG Lihe GUO Zhejin SHENG Jian FEI 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 *** 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 *** transgenic mice exhibited less reduction of striatal TH protein and number of TH positive neurons in the substantia nigra induced by 1-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 D *** striatal α-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 ofparkin may attenuate dopaminergic neurodegeneration induced by MPTP through protection of mitochondria and reduction of α-synuclein in the nigrostriatal pathway.

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

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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届会员代表大会

作者： Miao-Jun LAI Hua-Qiang ZHU Dan FU Wei-Sheng CHENG Han-Ting ZHANG Wen-Hua ZHOU Laboratory of Behavioral Neuroscience Ningbo Addiction Research and Treatment Center School of Medicine Ningbo University China 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 (250 μg/kg) was introduced for the reinstatement of heroin-seeking *** 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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Ionotropic glutamate receptors in medial prefrontal cortex and dorsal hippocampus are involved in different components of methamphetamine-induced 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届会员代表大会

作者： Wen-Yan HAN Fang WANG Shi-Yuan FU Ming SONG Ping DU Xiao-Long JING Chun-Fu WU Jing-Yu YANG Department of Pharmacology Shenyang Pharmaceutical University 110016 Shenyang China 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 drug-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-d-aspartate (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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Hippocampal neuronal nitric oxide synthase mediates the stress-related depressive behaviors of glucocorticoids by down-regulating glucocorticoid receptor

Hippocampal neuronal nitric oxide synthase mediates the stre...

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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： Qi-Gang ZHOU Li-Juan ZHU Chen CHEN Hai-Yin WU Chun-Xia LUO Lei CHANG Dong-Ya ZHU Department of Pharmacology School of Pharmacy Nanjing Medical University Nanjing 210029 China Department of Pharmacology School of Pharmacy Laboratory of Cerebrovascular Disease Nanjing Medical University Nanjing 210029 China

The molecular mechanisms underlying the behavioral effects of glucocorticoids are poorly *** report here that hippocampal neuronal nitric oxide synthase (nNOS) is a crucial *** mild stress and glucocorticoids exposures caused hippocampal nNOS overexpression via activating mineralocorticoid receptor (MR).In turn, hippocampal nNOS-derived nitric oxide (NO) significantly down-regulated local glucocorticoid receptor (GR) expression through both soluble guanylate cyclase (sGC)/cGMP and peroxynitrite (ONOO-)/extracellular signal-regulated kinase (ERK) signal pathways, and thence elevated hypothalamic corticotrophin-releasing factor (CRF), a peptide that governs the hypothalamic-pituitary-adrenal *** importantly, nNOS deletion or intrahippocampal nNOS inhibition and NO-cGMP signaling blockade (using NO scavenger or sGC inhibitor) prevented the corticosterone-induced behavioral modifications, suggesting that hippocampal nNOS is necessary for the role of glucocorticoids in mediating depressive *** addition, directly delivering ONOO-donor into hippocampus caused depressive-like *** findings reveal a role of hippocampal nNOS in regulating the behavioral effects of glucocorticoids.

关键词： hippocampal neuronal nitric oxide synthase glucocorticoid receptor glucocorticoids depression

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GRK5 mediates F-actin bundling and targets bundles to membrane to control neuronal morphogenesis

GRK5 mediates F-actin bundling and targets bundles to membra...

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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： Yuejun CHEN Feifei WANG Hui LONG Yin CHEN Ziyan WU Lan MA Pharmacology Research Center and the State Key Laboratory of Medical Neurobiology Shanghai Medical College and Institutes of Brain Science Fudan University Shanghai 200032 China

Neuronal morphogenesis requires extensive membrane remodeling and cytoskeleton *** we show that GRK5, a serine/threonine kinase of G protein-coupled receptors, is critically involved in neurite outgrowth, dendrite branching, and spine morphogenesis, through promoting filopodia ***, GRK5 is not acting as a kinase, but rather provides a key link between the plasma membrane and actin ***5 promotes F-actin bundling at membranes of dynamic neuronal structures through interacting with both F-actin and PI(4,5)***, coupling regulation of actin cytoskeleton dynamics and membrane remodeling is mediated by separate domains of GRK5 and is required for its effects on neuronal ***, GRK5 knockout mice exhibit immature spine morphology and deficient learning and *** findings reveal GRK5 as a critical mediator of dendritic development and suggest that coordinated actin cytoskeleton and membrane remodeling mediated by bifunctional actin-bundling and membrane-targeting molecules such as GRK5 is crucial for proper neuronal morphogenesis and the establishment of functional neuronal circuitry.

关键词： neuronal Morphogenesis G protein-coupled receptor kinases F-actin bundling actin cytoskeleton

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