从海马-杏仁核神经元PI3K/Akt/mTOR信号通路与细胞骨架关系探讨抑郁症发病机制

项目名称： 从海马-杏仁核神经元PI3K/Akt/mTOR信号通路与细胞骨架关系探讨抑郁症发病机制

项目编号： No.81201048

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： 刘昊

作者单位： 河北联合大学

项目金额： 23万元

中文摘要： 抑郁症发病率越来越高，已成为目前一个研究热点，但其具体发病机制尚未明确。研究提示海马和杏仁核体积结构异常是抑郁患者的典型症状之一，其原因可能与这些部位存在明显的神经细胞凋亡有关。PI3K/Akt/mTOR信号通路是调节凋亡的重要途径之一，细胞骨架是细胞功能和结构的基础，因此我们推测在抑郁症发病中海马、杏仁核神经元细胞骨架改变受PI3K/Akt/mTOR信号通路调控。本研究利用慢性不可预见性温和应激建立大鼠抑郁症模型，采用透射电镜等技术观察海马、杏仁核神经元超微结构变化；采用免疫组织化学、激光扫描共聚焦、免疫印迹及荧光原位杂交等技术检测海马、杏仁核神经元细胞骨架和PI3K/Akt/mTOR信号通路改变的关系。同时构建PTEN腺病毒，活体转染至抑郁症动物模型，观察过表达PTEN基因对细胞骨架和信号通路的影响，从而为揭示抑郁症发病过程中海马和杏仁核的结构变化及抑郁症发病机制研究提供实验依据。

中文关键词： 抑郁症；海马；杏仁核；细胞骨架；PTEN

英文摘要： Depression is one of the most typical stress disorders, and has progressively increased incidence, but its pathogenesis has not been clarified yet. It has been documented that significant reduced of hippocampus and amygdala volumes, one symptom of this disease, may be due to the enhanced neuronal apopotosis of these parts. It's well known that PI3K/Akt/mTOR signal pathway is one of the important ways to adjust apoptosis, and cytoskeleton is the foundation of cellular structure and function. Then we speculate that the cytoskeletonal changes of neuron in hippocampus and amygdala may be adjusted by PI3K/Akt/mTOR signal pathway. In this research, we will establish depression rat model by giving rats chronic unpredictable mild stress (CUMS), and observe the neuronal ultrastructure by using transmission electron microscope, detect the relationship between the cytoskeletonal changes and PI3K/Akt/mTOR signal pathway using immunohistochemistry, confocal laser scanning microscope (CLSM), Western-blotting and fluorescence in situ hybridization. In order to explore the role of PTEN, a key gene regulating cell proliferation and apoptosis, in this process, we attempt to construct the virus over-expressing PTEN, and transfect it to depression rat, and observe the effect of PTEN over-expression on cytoskeletion and signal pathw

英文关键词： depression；hippocampus；amygdala；cytoskeleton；PTEN