近年来，越来越多研究证明星形胶质细胞在维持大脑功能上起着更多的“主动”作用。ATP作为一种主要的胶质递质，参与调节突触传递、神经血管耦合，以及睡眠节律、抑郁情感等。星形胶质细胞释放ATP主要有两种途径：离子通道介导的递质释放和Ca2+依赖的溶酶体胞吐。其中，后者是星形胶质细胞ATP释放的主要方式。影响星形胶质细胞ATP释放的因素很多，但目前不清楚其调控机制。我们最新的研究提示，EET信号通路特异地调节星形胶质细胞ATP释放：EET信号通路通过激活溶酶体上的钙通道蛋白TRPML1，触发溶酶体的Ca2+释放，增加溶酶体胞吐活动，从而调控星形胶质细胞ATP释放。本项目拟采用分子生物学、实时荧光成像、电生理等技术/方法，针对星形胶质细胞ATP释放调节的关键环节开展研究，阐明EET信号通路对星形胶质细胞ATP释放的特异性调节机制，为研究胶质递质释放机制提供新思路，为发现抗抑郁新靶点等提供科学依据。

Mounting evidence had proved that astrocytes play an “active” role in maintaining brain function. As a major gliotransmitter, ATP is vital in regulating synaptic transmission, neurovascular coupling, as well as sleep and emotion. ATP release from astrocytes mainly depends on lysosome exocytosis. There are many factors that affect the release of ATP from astrocytes, such as mechanical stretch, chemical stimulation and hypoxia. However, the molecular mechanism underlying the modulation of ATP release by astrocytes is largely unknown. Our previous results and preliminary data suggested that epoxyeicosatrienoic acid (EET) signaling pathway specifically regulates ATP release from astrocytes. Soluble epoxide hydrolase (sEH), the key enzyme of EET signaling, is localized on lysosomes of astrocytes. Interestingly, the EET signaling regulates ATP release depends on lysosome exocytosis and TRPML1-mediated lysosomal calcium release is involved in EET signaling modulating ATP release. To test this hypothesis, the technologies/methods such as molecular biology, fluorescence imaging will be employed. The aim of the present study is to investigate the specific regulation of ATP release from astrocytes by EET signaling and reveal the underlying mechanism and to provide new insights for studying gliotransmitter release and novel targets for developing anti-depressants.