Calhm2 governs astrocytic ATP releasing in the development of depression-like behaviors
Calhm2 governs astrocytic ATP releasing in the development of depression-like behaviors
复制标题
Calhm2 在抑郁样行为的发展过程中控制星形胶质细胞 ATP 释放
DOI：
10.1038/mp.2017.229
复制
发表时间：
2018-04-01
影响因子：
11
通讯作者：
Zengqiang, Y.
中科院分区：
文献类型：
--
作者：
Jun, M.;Xiaolong, Q.;Zengqiang, Y.
细胞外ATP是脑中广泛存在的细胞间信号分子，在脑中其通过激活胶质细胞和神经元而作为神经调质发挥作用。虽然ATP对突触可塑性和神经胶质细胞相互作用以及情绪障碍具有多种作用，但ATP释放的来源和调节仍有待详细阐述。在这里，我们定义Calhm2作为ATP释放通道蛋白的基础上，在体外和体内模型。Calhm 2的常规敲除和条件性星形胶质细胞敲除均导致小鼠ATP浓度显著降低、海马棘数目减少、神经功能障碍和抑郁样行为，这些都可以通过ATP补充来显著挽救。我们的研究结果确定Calhm2作为一个重要的ATP释放通道，调节神经活动和抑郁症的潜在危险因素。
Extracellular ATP is a widespread cell-to-cell signaling molecule in the brain, where it functions as a neuromodulator by activating glia and neurons. Although ATP exerts multiple effects on synaptic plasticity and neuro-glia interactions, as well as in mood disorders, the source and regulation of ATP release remain to be elaborated. Here, we define Calhm2 as an ATP-releasing channel protein based on in vitro and in vivo models. Conventional knockout and conditional astrocyte knockout of Calhm2 both lead to significantly reduced ATP concentrations, loss of hippocampal spine number, neural dysfunction and depression-like behaviors in mice, which can be significantly rescued by ATP replenishment. Our findings identify Calhm2 as a critical ATP-releasing channel that modulates neural activity and as a potential risk factor of depression.