G蛋白偶联受体信号分子调控成年神经发生的研究

项目名称： G蛋白偶联受体信号分子调控成年神经发生的研究

项目编号： No.31270034

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 来滨

作者单位： 复旦大学

项目金额： 80万元

中文摘要： 成年神经发生理论颠覆了以往成年动物脑内没有神经元新生的传统观点，成年神经干细胞的增殖，自我更新和分化等行为受到干细胞本身及其周围微环境的精确调控，但是其分子机制不清楚。申请人一直从事GPCR信号分子GRK和arrestin的功能研究，并提前完成了青年基金项目GRK调控神经元树突发育机制的研究。进一步的研究发现GRK和arrestin基因敲除小鼠SGZ区成年神经干细胞增殖明显受损；成年神经发生相关行为学检测发现，arrestin基因敲除小鼠的情绪调控异常，焦虑抑郁样行为增加。提示GRK和arrestin可能是成年神经发生的重要调控分子。我们拟利用GRK，arrestin基因敲除小鼠和条件性敲除小鼠，结合神经干细胞特异表达Cre (Nestin-CreER)和星形胶质细胞特异表达Cre (S100b-CreER)的工具鼠，进一步研究GRK和arrestin在成年神经发生中的作用及机制。

中文关键词： arrestin 1；神经发生；海马；；

英文摘要： Adult neurogenesis, a process of generating functional neurons from adult neural precursors, occurs throughout life in restricted brain regions. The proliferation, self-renewal and differentiation of adult neural stem cells are precisely controlled by their intrinsic signals and their microenvironment. However, little is known about its underlying mechanisms. G protein-coupled receptor kinases (GRK) and beta-arrestins serve as negative regulators of GPCR signaling. In the current study, We found that GRK knockout mice, as well as beta-arrestin knockout mice, demonstrate defects in the proliferation of neuronal stem cells in the subgranular zone (SGZ) of the dentate gyrus (DG) in the hippocampus. Further behavioral examinations reveals that beta-arrestin knockout mice exhibit increased anxiety- and depression-like behaviors, which have been previously associated with defects in hippocampal neurogenesis. These findings suggest potential roles of GRK and beta-arrestin in adult neurogenesis. Using GRK or beta-arrestin knockout mice, GRK or beta-arrestin conditional knockout mice, and mice expressing a tamoxifen inducible Cre recombinase under the Nestin promoter or S100b promoter, we proposed to further explore the role of GRK and beta-arrestin in adult neurogenesis.

英文关键词： arrestin 1；Neurogenesis；hippocampus；；