星形胶质细胞CysLT1R与抑郁症的相关性及机制研究

One of the most important reasons is that key molecules have not been confirmed why a breakthrough has not been made for low toxicity and high efficacy of new antidepressant research. Our recent studies showed that cysteinyl leukotriene receptor 1(CysLT1R) might mediate the onset of depression. This study will use GFAP-initiated CysLT1R RNA interference lentiviral vector (LV-GFAPpro-CysLT1R shRNA-EGFP) and CysLT1R RNA lentiviral vector (LV-GFAPpro-CysLT1R-EGFP) for knock-down and over-expression of CysLT1R gene in mouse hippocampal astrocytes, as well as the Cre-LoxP recombinase system for conditional knockout of CysLT1R gene in astrocytes of mouse brain, to investigate the role of CysLT1R in physiological and pathological conditions of depression and its regulation of glutamate circle, brain-derived neurotrophic factor and inflammatory factors. The correlation between astrocyte CysLT1R and depression and its underlying mechanisms will be revealed from in vivo, in vitro and molecular level, which provides an important molecular target for the study of novel antidepressants based on the regulation of astrocyte function.

低毒高效新型抗抑郁药研究至今未获得突破，重要原因之一是未确立引发抑郁症的关键分子。我们近期研究显示，星形胶质细胞半胱氨酰白三烯受体1(CysLT1R)可能介导抑郁症的发病过程。本研究拟分别采用GFAP启动的CysLT1R RNA干扰慢病毒载体（LV-GFAPpro-CysLT1R shRNA-EGFP）和CysLT1R RNA慢病毒载体（LV-GFAPpro-CysLT1R-EGFP），敲减、过表达小鼠海马星形胶质细胞CysLT1R；采用Cre-LoxP重组酶系统条件性敲除小鼠脑内星形胶质细胞CysLT1R，探究CysLT1R在生理及抑郁症病理条件下的功能及其对突触间谷氨酸循环、脑源性神经生长因子和炎症因子的调节作用，从在体、离体及分子水平证明星形胶质细胞CysLT1R与抑郁症的相关性及机制，为基于星形胶质细胞功能调节研究新型抗抑郁药提供重要的分子靶标。