G蛋白偶联受体激酶5在小鼠社会交互行为中的作用及机制研究

项目名称： G蛋白偶联受体激酶5在小鼠社会交互行为中的作用及机制研究

项目编号： No.31270027

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： 王菲菲

作者单位： 复旦大学

项目金额： 80万元

中文摘要： 社会交互障碍是孤独症的重要表型，往往伴随着神经系统发育异常。包括神经元结构功能的异常和神经内分泌系统的改变。目前对于调控社会交互行的具体生物学机制仍不清楚。G蛋白偶联受体激酶5（G protein coupled receptor kinases, GRK5）是GPCR信号通路中的重要调控分子。我们的研究表明GRK5通过调控细胞骨架和受体信号转导等多种生物学机制调控神经系统发育，我们前期结果显示GRK5 基因敲除小鼠和陌生小鼠接触时间变短，表现出社会交互障碍。这些结果提示GRK5可能通过调控神经系统发育如突触结构可塑性调节社会交互行为，但其具体分子机制不清楚。本项目将围绕GRK5调控社会交互行为的具体分子机制，采用形态学，行为学和电生理等多种研究手段进行研究。我们的研究成果将为社会交互行为的调控提供新的神经生物学机制。

中文关键词： G蛋白偶联受体激酶；神经发育；突触可塑性；社会识别记忆；成瘾

英文摘要： Social deficits are the important phenotypes of autism, and are related with the abnormalities of neuronal development, including the deficiency of neuronal structure and function, as well as the alteration of neuronal endocrinology. However, the molecular mechanisms of social deficits remain largely unknown. G protein coupled receptor kinases (GRK5) is an important modulator of GPCR signaling pathway. Our previously studies have demonstrated that GRK5 regulates the development of neuronal system through multiple mechanisms, such as cytoskeleton and receptor signaling transduction regulation. Furthermore, we also found that the social interaction and social novelty in GRK5 knockout mice were impaired, indicating GRK5 regulates social behavior，and may probably via its regulation of neuronal development, including the regulation of dendrite structure and plasticity. Thus, we will carry out behavior, immunohistochemistry and electrophysiology to study the molecular mechanism of GRK5 in social behavior regulation, and will provide new biological mechanisms for the regulation of social behavior.

英文关键词： G protein receptor kinase；neuronal development；synapse plasticity；social recognition；addiction