腹侧被盖区GABA通路对缺血海马新生神经发生的影响及机制

项目名称： 腹侧被盖区GABA通路对缺血海马新生神经发生的影响及机制

项目编号： No.81471334

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 承欧梅

作者单位： 重庆医科大学

项目金额： 70万元

中文摘要： 急性全脑缺血可造成海马和皮层锥体神经元死亡，纹状体小清蛋白阳性的γ-氨基丁酸(PV+GABA）中间神经元及多巴胺投射纤维数量明显减少。海马神经发生在脑功能重建中起到了重要作用。腹侧被盖区（VTA）是重要的睡眠调节中枢，近来研究发现VTA含有的GABA中间神经元接受来自前额叶、纹状体等的抑制性输入，除提供了局部抑制，也投射到海马、伏隔核等，VTA的GABA中间神经元的远程抑制性投射海马的细胞靶点和功能尚不明确，预实验发现短期睡眠剥夺可提高缺血大鼠的空间记忆能力。结合以往研究，申请者认为VTA的GABA通路可能参与了海马神经发生的调控。本课题拟从新生神经干细胞激活数量、分化成熟的比率和整合功能等方面研究VTA的GABA通路对新生神经发生的影响。采用结构成像结合电生理学技术研究GABA远程投射的细胞靶点和功能，以期揭示VTA远程调控神经发生的途径与机制，为缺血性脑损害提供新的治疗途径。

中文关键词： 神经干细胞；脑缺血；神经康复；神经再生；神经元

英文摘要： Pyramidal neurons in hippocampal and cortical selectively died and the number of parvalbumin positive γ- aminobutyric acid (PV + GABA) interneurons and dopamine projection fibers in striatum significantly reduced following global cerebral ischemia . Hippocampal neurogenesis plays an important role in the brain recovery. Ventral tegmental area (VTA) is one of important center for sleep regulation. Recently, it has been reported that VTAGABA interneuron, which receives inhibitory input from the prefrontal cortex , striatum, nucleus accumbens, not only provide a partial inhibition, but also projecte to the hippocampus, nucleus accumbens. It is not yet clear which is inhibitory long projection target cells of GABA interneurons to hippocampus. Our preliminary study discovered that short-term sleep deprivation can improve the global ischemia rat`s space memory capacity . Based on previous studies, It is hypothesized the VTA GABA pathway may be involved in the regulation of hippocampal neurogenesis. This project intends to discover the effect of VTA GABA pathway on the number, the rates of differentiation and maturation and the function of integration of new adult-born stem cells in the hippocampus. In order to reveal pathways and mechanisms of VTA remote regulating neurogenesis, which will provide a new therapeutic approach for ischemic brain damage, the electrophysiological and structural imaging techniques will been applied to study cellular targets and functions of GABA remote projection.

英文关键词： neurnal stem cell;Ischemia;neurological rehabilitation;Neurogenesis;Neuron