2-AG及内源性大麻素1型受体在电针抗抑郁作用中的机制研究

抑郁症严重影响人类健康和生活质量，探讨其发病机制并开发新的治疗策略是本领域的研究重点。国内外同行和申请人的前期研究均证实电针具有抗抑郁作用，但其机制还有待阐明。海马内源性大麻素系统在调节抑郁样行为中具有重要作用，申请人新近的研究发现：电针可通过上调海马2-AG和内源性大麻素1型受体（CB1R）发挥情绪调节功能。预实验亦发现电针可上调海马2-AG/CB1R，改善其突触可塑性和抑郁样行为，而该作用可被CB1R抑制剂（AM251）所阻断。我们认为：电针干预可能通过激活海马2-AG/CB1R，改善其神经发生和突触可塑性，从而发挥抗抑郁作用。为此本课题以2-AG水解酶和合成酶以及CB1R基因敲除小鼠为研究平台，综合运用电生理、病毒转染、分子生物学和行为学检测等技术手段，阐明电针调节海马2-AG/CB1R的细胞与分子机制，为电针干预治疗抑郁症提供理论依据，为优化抑郁症的治疗策略提供细胞和分子靶点。

Depression seriously affects human health and quality of life and the exploration of its pathogenesis and the development of new treatment strategies have been the research focus in the field of psychiatry. Previous studies confirmed the antidepressant effect of electroacupuncture (EA), but its mechanism remains to be elucidated. The endogenous cannabinoid system in the hippocampus plays an important role in the regulation of depressive-like behavior. Our recent studies have found that electroacupuncture can regulate mood by up regulating hippocampal 2-arachidonoylglycerol (2-AG) and Cannabinoid receptor 1 (CB1R). Moreover, we also found that EA could up regulate hippocampal 2-AG/CB1R, improve its synaptic plasticity as well as depressive-like behaviors, which could be blocked by CB1R inhibitor (AM251). We deduce that EA intervention may exert its antidepressant effects by activating the 2-AG/CB1R in the hippocampus and improving its neurogenesis and synaptic plasticity. Therefore, this project plan to use 2-AG hydrolase and synthetase and CB1R gene knockout mice as the research platform, and comprehensively uses electrophysiology, virus transfection, molecular biology and behavioral test techniques to clarify the cellular and molecular mechanism of EA. This project will uncover theoretical basis for EA intervention in the treatment of depression, and provide cellular and molecular targets for the optimization of treatment strategies for depression.