mTOR信号通路在痛相关海马突触可塑性中的作用

项目名称： mTOR信号通路在痛相关海马突触可塑性中的作用

项目编号： No.81200851

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 神经系统疾病、精神疾病

项目作者： 吕丹

作者单位： 天津市第一中心医院

项目金额： 23万元

中文摘要： 哺乳动物雷帕霉素靶蛋白(mTOR)是一种重要的调节蛋白，可调控翻译元件的生物合成。mTOR依赖的局部蛋白合成在慢性痛所致外周伤害性感受器的敏化及脊髓背角神经元可塑性中起关键作用,但在痛相关海马突触可塑性中的作用尚待阐明。前期工作证实，外周持续性伤害可诱导海马结构发生突触效能和空间联系的可塑性改变。我们推测，mTOR 信号通路可被持续性痛激活,通过局部蛋白质翻译机制调控大鼠海马突触可塑性。本课题采用分子生物学、电生理以及行为学方法进行以下研究：(1)明确mTOR信号通路在海马结构中的分布特点；(2)揭示持续性痛刺激条件下mTOR 信号通路mRNA和蛋白表达的变化规律；(3)在神经元网络水平上，明确mTOR信号通路是否介导持续性痛所致海马突触可塑性改变；(4)进一步验证海马mTOR信号通路介导大鼠痛相关行为的改变。为临床上治疗慢性痛患者所伴发的认知和精神障碍提供新的靶点。

中文关键词： mTOR信号通路；雷帕霉素；突触可塑性；海马；炎性痛

英文摘要： Recent studies indicate that mTOR, as an important regulating gene, controls cellular growth and proliferation and formation of synaptic plasticity by regulating synthesis of many kinds of proteins. Therefore, the study of revealing the key roles of mTOR in the generation of central and peripheral sensitization of pain becomes a hot spot.Our previous work proved that peripheral persistent nociception has great impact upon the higher brain structures，which not only temporal, but also lead to spatial plasticity of synaptic interconnections and functions in the hippocampal formation by multi-electrode array recording system. Moreover, two kinds of group I metabotropic glutamate receptor (mGluR1 and 5) take part in this process was demonstrated . Based on the previous work in our lab, we make further exploration in the mechanisms of mTOR signaling pathway in the persistent pain-associated spatial and temporal changes in entorhinal-hippocampal synaptic plasticity. The experiment of this study design as follows:(1) Distribution of mTOR and phospho-mTOR in rat hippocampal formation will be observed by immunofluorescence double labeling of mTOR in the DG and CA1 area.(2) Activation of mTOR signaling pathway in rat hippocampus tissues induced by peripheral persistent pain will be detected by western blotting.(3) We will

英文关键词： mTOR signaling pathway；Rapamycin；Synaptic plasticity；Hippocampal；inflammatory pain