抑郁症严重危害人类健康，到2020年可能成为仅次于心血管疾病的世界第二大疾病。近年来研究表明星形胶质细胞病理改变和功能障碍可能是抑郁症重要的病理生理机制之一，然而星形胶质细胞介导的神经炎症与细胞死亡在抑郁症发生发展中的作用及机制并不明确。本项目拟在前期发现抑郁症模型小鼠大脑皮层、海马等脑区星形胶质细胞数量减少并伴有Caspase-1活化的基础上，应用Caspase-1敲除小鼠和NLRP3条件敲除小鼠进一步研究星形胶质细胞的炎症反应和焦亡与抑郁症发病的相关性，在整体、细胞和分子水平系统研究、阐明星形胶质细胞NLRP2/NLRP3/AIM2炎症小体介导的炎症因子IL-1β/IL-18释放和细胞焦亡在抑郁症发生发展中的作用及机制，揭示星形胶质细胞存活和功能在抗抑郁治疗中的作用和意义。预期研究成果不仅有助于深化对抑郁症病理机制的认识，也为研发靶向星形胶质细胞功能调控的抗抑郁症药物提供新的思路。

Depression is a serious mental disorder in the world, but the underlying mechanisms remain unclear and the effective cures are scarce. Currently, it has been recognized that pathological changes and dysfunction of astrocytes play crucial roles in the pathogenesis of depression. However, the effects of astrocyte-mediated neuroinflammation and cell death in depression are still unclear. Our previous study showed that the number of astrocytes was reduced and caspase-1 was activated in the cortex and hippocampus of CMS model mice. Therefore, this work is designed to further explore the association of astrocytic pyroptosis and inflammation with depression by caspase-1 knockout and NLRP3 conditional knockout mice. Next we will clarify the roles of astrocytic NLRP2/NLRP3/AIM2 inflammasomes on IL-1β/IL-18 production and pyroptosis in the pathogenesis of depression. Furthermore, the significance of astrocyte survival and function in anti-depressive treatment will be demonstrated in this study. Together, our findings will help us to deepen the understanding of depression pathogenesis, and will provide potential and ideal targets for the development of drugs to treat depression.