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NAD+ treatment decreases spontaneous recurrent seizures and brain injury of pilocarpine-induced epilepsy model mice

NAD+ treatment decreases spontaneous recurrent seizures and ...

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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： Zhe SUN,Jue-Gang JU,Sheng-Tian LI~* Laboratory of Synaptic Signaling and Behavioral Neurosciences,School of Life Sciences and Biotechnology,Shanghai Jiao Tong University,Shanghai 200240,China

Objective Epilepsy is a major neurological disease characterized by *** 30%of people with epilepsy are not responsive to the treatment even to the best available ***,it is of great theoretical and clinical significance to investigate the mechanisms underlying epilepsy,and to search for effective ***+ is a fundamental molecule in cells,which has been shown to decrease oxidative and excitotoxic cell death as well as ischemic brain *** the current study,we tested the effect of NAD+ on pilocarpine-induced *** NAD+(100 mg/kg) or vehicle was *** 1 h after the onset of pilocarpine-induced status epilepticus(SE) in male C57BL/6J mice(25-30 g,7 weeks of age).Induction of spontaneous recurrent seizures (SRS) was recorded by EEG recording technique in freely moving mice at two weeks *** We found that NAD+ treatment markedly decreases the number of spontaneous epileptiform EEG *** using histological techniques,we also found that NAD+ treatment reduces the brain injury in the pilocarpine-induced epilepsy model *** Our study suggested a therapeutic potential of NAD+ for epilepsy.

关键词： NAD treatment decreases spontaneous recurrent seizures and brain injury of pilocarpine-induced epilepsy model mice

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The influence of anxiety on the framing effect

The influence of anxiety on the framing effect

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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： Ruolei GU,Yuejia LUO~* State Key Laboratory of Cognitive Neuroscience and Learning,Beijing Normal University,Beijing 100875,China *Corresponding author

Objective Studies on the framing effect indicate that people tend to make risk-avoidant decisions when the choice is framed(***) as a choice between gains,but make risk-seeking decisions when it is framed as a choice between *** far,the role of anxiety and/or depression in decision-making under framing situations is *** examined the impact of anxiety and depression on the framing effect with a classical monetary gambling *** Participants were instructed that they would have to select either a "sure" or "gamble" *** gain frame trials,the sure option was presented as money retained;in loss frame trials,it was presented as money *** participants' decision-making was coded as the proportion of sure option choices for each *** Anxiety,but not depression,had significant effects on framing-related *** levels of anxiety were correlated with stronger framing effects;most interestingly,high-anxious subjects were more risk-seeking in the loss frame compared to low-anxious subjects,which conflicts with previous findings that high-anxious people are consistently more *** The current findings provide evidences that,in contrast with bipolar/ tripolar theoretical models which suggest that all same-valence emotions produce similar cognitive effects,anxiety and depression induce distinct impacts on decision-making.

关键词： decision making framing effect emotion anxiety depression

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Tbx3 and Ptfla determine the expression of receptors of neurotransmitters and nueropeptides in the dorsal spinal cord

Tbx3 and Ptfla determine the expression of receptors of neur...

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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： Zhen GUO,Jing-Wen NING,Yi-Wen BU,Ying CHEN,Zhi-Qin XIE,Xiao-Lin ZHAO,Guan-Nan XIA, Le-Ping CHENG~* Institute of Neuroscience,Shanghai Institutes for Biological Sciences,Chinese Academy of Science,Shanghai 200031, China

Neurotransmitters and neuropeptides are of most importance in vertebrate central nervous system,which mediate most of the excitatory and inhibitory neural *** evoke postsynaptic electrical responses by binding to members of a repertoire of their receptors,which excite or inhibit *** between the excitation and inhibition within dorsal horn neurons of the spinal cord may lead to chronic *** and others' previous studies have showed that transcription factors Tlx1/3 and Ptf1a control the neurotransmitter phonotype of excitatory and inhibitory neurons respectively in the dorsal spinal *** we analyzed the expression of some neurotransmitters' and neuropeptides' receptors in the dorsal spinal cord of the developing mouse embryos using in situ hybridization and fate mapping *** found most of the receptors were expressed in the dorsal horn,some of which had specific expression ***,we found Tlx1/3 and Ptf1a were required for the expression of some selected receptors,while dispensable for most of other *** studies thus show that specific receptors are subject to local master transcription factors regulation and at the mean time provide several theoretical pain control targets in the dorsal spinal cord.

关键词： receptors Tlx3 Ptfla Lbxl Pax2 dorsal horn spinal cord

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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次会员代表大会

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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Kv7/KCNQ channels are functionally expressed in oligodendrocyte progenitor cells

Kv7/KCNQ channels are functionally expressed in oligodendroc...

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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 WANG,Xiao-Fei GAO,Lin XIAO,Zheng-Hua XIANG,Cheng HE~* Institute of Neuroscience and Key Laboratory of Molecular Neurobiology of Ministry of Education,Second Military Medical University,Shanghai 200433,China

Objective K7/KCNQ channels are widely expressed in neurons and they have multiple important functions,including control of excitability,spike afterpotentials,adaptation,and theta *** in KCNQ genes have been demonstrated to associate with human neurological ***,little is known about whether K7/KCNQ channels are expressed in oligodendrocyte lineage cells（OLCs）and what their functions in OLCs. The present study is aim to explore the expression and functions of K7/KCNQ channels in *** In this study,we characterized K7/KCNQ channels expression in rat primary cultured OLCs by RT-PCR,immunostaining and *** function of K7/KCNQ channels in OPCs motility was performed by Boyden chamber migration assay in ***（1）K7.2-5/ KCNQ2-5 channels expressed in OLCs.（2）The inhibition of K7/ KCNQ channels promoted OPCs motility in *** These findings showed that K7/KCNQ channels were functionally expressed in rat primary cultured OLCs and might play an important role in OPCs functioning in physiological or pathological conditions.

关键词： KCNQ potassium channels oligodendrocyte progenitor cells cell motility

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Glutamate activated spinal astrocytes are involved in the thermal hyperalgesia

Glutamate activated spinal astrocytes are involved in the th...

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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： Rui-Hong SHI,Xin ZHAO,Ce ZHANG~* Department of Physiology National Key Disciplines,Key Laboratory for Cellular Physiology of Ministry of Education,Shanxi Medical University,Taiyuan 030001,China

Objective Numerous evidence suggests that spinal astrocytes play an important role in chronic pain through release of neuroactive substances,such as interleukin and *** produces marked effects in initiation and transmission of nociceptive ***,there is a lack of direct evidence that how glutamate activate astrocytes and what's effects of activated astrocytes by glutamate on pain *** study therefore explored the direct effects of glutamate activation of spinal *** Primary culture of spinal astrocytes were administered with *** levels of protein and mRNA expression of IL-6,which reflect astrocyte activation, were determined by ELISA assay and real-time *** spinal astrocytes activated by glutamate were injected into the lumber enlargement of adult Wistar rats,and paw withdrawal latency(PWL) was *** Administration of glutamate(1 000 uM) activated astrocytes from 6 h after intrathecal injection and reached the maximal level at 24 h(the last time point we explored).Besides,glutamate(1 000 uM) enhanced the release of IL-6 by astrocytes. Intrathecal injection of cultured spinal astrocytes,which were stimulated by glutamate,induced a substantial decrease of PWL,indicating the development of thermal *** Our results suggest that activated astrocytes by glutamate is sufficient to produce thermal hyperalgesia in rats by releasing IL-6.

关键词： glutamate spinal astrocyte thermal hyperalgesia IL-6

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Activation of KCNQ potassium channels by small chemical moleculars

Activation of KCNQ potassium channels by small chemical mole...

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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： Zhaobing GAO~1,Min LI~(1,2) 1 State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences,555 Zu Chong Zhi Road,Zhangjiang Hi-Tech Park,Shanghai 201203,China 2 Department of Neuroscience,High Throughput Biology Center and Johns Hopkins Ion Channel Center,School of Medicine,Johns Hopkins University,Baltimore,Maryland 21205

KCNQ potassium channels play a critical role in controlling membrane *** a typical voltagegated ion channels(Kv),KCNQ channels undergo closed to open transitions by sensing transmembrane potential changes and mediate inhibitory potassium *** of KCNQ channel activity as results of genetic mutation is causal to a variety of human diseases including epilepsy,arrhythmia and ***,discovery of small compounds to activate voltage-gated ion channels is an important strategy for clinical intervention in human diseases caused by membrane hyperexcitability,including anxiety,epilepsy,arrhythmia and neuropathic *** the binding of these molecules induces a conformational change leading to the opening of these channels,there is also a considerable conceptual interest in understanding the molecular basis of these "gain of a function" *** molecule activators of cation channels are rare;however,several novel compounds have been identified for KCNQ potassium ***,we reported two new molecules which potentiate either cardical or neuronal KCNQ channels and identified molecular determinants for their activity,which provide exciting insights into activation of voltage-gated channels by small molecuars.

关键词： Activation of KCNQ potassium channels by small chemical moleculars

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过表达α-synuclein98诱导PC12细胞氧化应激及对鱼藤酮敏感性增强

过表达α-synuclein98诱导PC12细胞氧化应激及对鱼藤酮敏感性增强

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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：宋连昆马开利苑玉和韩宁陈乃宏中国医学科学院、北京协和医学院药物研究所

目的α-synuclein是帕金森病人路易小体的主要组成成分,并且在家族性帕金森病人中发现存在该蛋白的基因突变,说明α-synuclein与帕金森病密切相关。研究发现,路易小体中存在α-synuclein C端截短体,但其对细胞的作用机制尚不明确。杀虫... 详细信息

目的α-synuclein是帕金森病人路易小体的主要组成成分,并且在家族性帕金森病人中发现存在该蛋白的基因突变,说明α-synuclein与帕金森病密切相关。研究发现,路易小体中存在α-synuclein C端截短体,但其对细胞的作用机制尚不明确。杀虫剂鱼藤酮可能是诱发帕金森病的一种环境毒剂,它能导致线粒体功能障碍,增强细胞氧化应激,并且研究认为氧化应激也促进了帕金森病的发病。α-synuclein98是最近发现的一种C端截短体,本实验通过在PC12细胞中过表达α-synuclein98蛋白,研究该截短体对PC12细胞的毒性作用及过表达α-synuclein98蛋白的PC12细胞对鱼藤酮敏感性的变化。方法通过PCR方法获得α-synuclein全长和98的基因片段,克隆到DsRed-N1载体并转染PC12细胞,G418筛选稳定细胞株,RT-PCR与Western Blotting验证细胞稳定表达α-synuclein全长和198截短体;MTT法测定细胞活力;活性氧检测试剂盒和脂质氧化试剂盒测定胞内ROS和MDA水平。结果（1）获得稳定表达α-synuclein全长和98截短体的PC12细胞株。（2）MTT结果表明在没有鱼藤酮刺激的条件下,过表达α-synuclein98对pC12细胞活力没有明显抑制作用（对照组的95%）。（3）过表达α-synuclein98 PC12细胞内ROS与MDA水平相比对照组分别提高了26.5%和149.8%（P＜0.05）,而过表达全长α-synuclein的分别提高了5.6%与15.6%。（4）在0.5、1、2、5μM鱼藤酮刺激24 h后,过表达α-synuclein98的细胞活力明显降低（P＜0.05）,并呈浓度依赖性。结论过表达α-synuclein98能增加PC12细胞氧化应激水平,明显增强细胞对鱼藤酮的敏感性,导致细胞活力下降。

关键词： α-synuclein98 ROS MDA 氧化应激鱼藤酮细胞活力

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化合物CH03对LPS激活小胶质细胞BV2炎症的影响

化合物CH03对LPS激活小胶质细胞BV2炎症的影响

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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：宋修云胡金凤陈乃宏中国医学科学院药物研究所北京100050

目的化-物CH03是我所自主研究开发的新型小分子化合物,本实验室前期研究发现其对多种诱导剂所致神经细胞损伤均具有显著改善作用.本研究旨在观察化合物CH03对脂多糖(LPS)所致小鼠小胶质细胞瘤细胞BV2激活的抑制作用.方法 100 ng/mL LP... 详细信息

目的化-物CH03是我所自主研究开发的新型小分子化合物,本实验室前期研究发现其对多种诱导剂所致神经细胞损伤均具有显著改善作用.本研究旨在观察化合物CH03对脂多糖(LPS)所致小鼠小胶质细胞瘤细胞BV2激活的抑制作用.方法 100 ng/mL LPS作用BV2细胞构建神经炎症细胞模型,采用可见光观察、MTT法、ELISA、Gress法、DCF-DA荧光探针、Western Blot、免疫荧光检测化合物CH03 (0.1,1,10 μmol/L)对BV2细胞激活的影响.结果形态学观察结果表明,LPS模型组细胞呈阿米巴状,1、10 μmol/L CH03组,细胞折光度良好,阿米巴状细胞数明显减少.MTT结果表明,与空白对照及LPS组比较,CH03各剂量对细胞存活率均无显著影响,说明CH03对静息及活化状态下的BV-2细胞存活率均无显著影响.ELISA结果显示,LPS组的细胞培养上清中nF-α、IL-1β量分别为2059±33 pg/mL、169±5pg/mL(空白对照组为54±14 pg/mL、58±11pg/mL),而0.1、1、10 μmol/L CH03组TNF-α含量分别为2065±12 pg/mL、1954±28 pg/mL、1506±35 pg/mL,IL-1β含量分别为172±6 pg/mL、130±6 pg/mL、88±8 pg/mL,即1、10 μmol/L CH03均能显著抑制炎症因子TNFα、IL-1β的释放.Gress实验结果表明,LPS组细胞培养上清中NO含量为100.0％±0.5％(空白对照组28.9％±0.5％),0.1、1、10 μmol/L CH03组NO含量分别为95.7％±1.6％、89.4％±1.7％、79.1％±4.2％,即CH03可显著抑制LPS诱导的BV2细胞生成***-DA荧光探针检测胞内ROS结果显示,1、10 μmol/L CH03组细胞绿色荧光强度较LPS组显著降低.Western Blot、免疫细胞荧光结果显示,CH03可剂量依赖性抑制LPS诱导的NF-κB/p65入核,抑制JNK、p38的磷酸化,抑制iNOS、COX-2胞内表达.即CH03可通过抑制NF-κB入核、MAPK通路的活化,抑制炎症蛋白iNOS、COX-2表达,进而抑制炎症因子ROS、NO、TNF-α、IL-1β的生成.结论化合物CH03对LPS所致BV2细胞炎症具有明显保护作用,提示CH03可能具有抗神经炎症的作用,对于对抗神经退行性疾病的研究可能具有重要意义.

关键词：化合物CH03 脂多糖 BV2细胞神经炎症

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HMGB1的两种亚型具有不同调节功能

HMGB1的两种亚型具有不同调节功能

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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：王勇军董莹莹宦有娟丁斐硕晓松南通大学江苏省神经再生重点实验室南通226001

目的近年来研究发现,免疫细胞可以被动或主动释放高迁移率族蛋白HMGB1,进而调节炎症反应.同时也有研究认为,HMGB1促进神经元细胞黏附和轴突生长,参与神经系统的发育和成熟.然而这两种矛盾的生物学功能如何在同一分子中得到统一,一直令... 详细信息

目的近年来研究发现,免疫细胞可以被动或主动释放高迁移率族蛋白HMGB1,进而调节炎症反应.同时也有研究认为,HMGB1促进神经元细胞黏附和轴突生长,参与神经系统的发育和成熟.然而这两种矛盾的生物学功能如何在同一分子中得到统一,一直令人疑惑.我们以多疣壁虎为实验模型,克隆了HMGB1基因的两个亚型HMGB1a和HMGB1b,本实验拟对这两个不同亚型基因进行功能比较研究.方法壁虎腹腔注射LPS以及断尾再生研究HMGB1a和HMGB1b的表达;以RAW264.7巨噬细胞株和神经母细胞瘤进行体外表达分析以及功能位点的突变分析.结果 (1)同源比对发现,HMGB1a和HMGB1b的主要功能域仅有一个氨基酸不同.壁虎断尾再生模型研究发现,HMGB1a和HMGB1b主要定位于脊髓的灰质,断尾损伤后HMGB1b的表达呈明显上调,而HMGB1a的表达丰度在断尾损伤后没有显著性差异;(2) LPS腹腔注射模型显示,在主要免疫调节器官脾脏以及肾和肝中,HMGB1a的表达随着处理时间的延长,呈逐渐上升趋势,而HMGB1b在各组织中表达变化无明显差异;(3)体外实验结果显示,在RAW264.7巨噬细胞株中过表达HMGB1a后,免疫因子TNF-α、IL1-a表达量显著上调,而过表达HMGB 1b后免疫因子TNF、IL1a表达量不发生明显变化;对活性位点的氨基酸互换突变后发现,过表达HMGB1am其效应与HMGB1b类似,而过表达HMGB1bm后效应与HMGB1a类似;(4)在神经元细胞中的研究发现,过表达HMGB1b后,神经元细胞Bc1-2/Bax显著升高,而过表达HMGB31a则没有显著变化,活性位点的氨基酸进行互换突变后过表达发现,HMGB1a和HMGB1b的功能也发生互换.研究表明,HMGB1a和HMGB1b主要通过TLR2和TLR4受体起作用.结果提示,HMGB1a和HMGB1b分别与免疫调节和神经元抗凋亡有关,哺乳动物中的HMGB1促进神经再生以及介导免疫调节,可能由HMGB1的不同亚型调节.

关键词：壁虎 HMGB1 亚型凋亡炎症

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