Gap junction channels as potential targets for the treatment of major depressive disorder
Gap junction channels as potential targets for the treatment of major depressive disorder
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间隙连接通道作为治疗重度抑郁症的潜在靶点
DOI：
10.1007/s00213-017-4782-7
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发表时间：
2018
影响因子：
3.4
通讯作者：
Chen Nai-Hong
中科院分区：
文献类型：
--
作者：
Ren Qian;Wang Zhen-Zhen;Chu Shi-Feng;Xia Cong-Yuan;Chen Nai-Hong
背景重度抑郁症（MDD）仍然是世界范围内的一个主要公共卫生问题。 MDD 与神经胶质细胞（尤其是星形胶质细胞）间隙连接通道（GJC）功能障碍之间的关联仍存在争议。目的本综述概述了星形胶质细胞 GJC 在 LMDD 中的作用。结果暴露于慢性不可预测的应激导致大鼠前额皮质连接蛋白表达减少，这一结果与 MDD 患者大脑尸检研究报告的临床结果。这些大鼠的长期抗抑郁治疗增加了连接蛋白的表达。然而，正常啮齿动物的药理学 GJC 阻断会降低连接蛋白的表达并引起抑郁样行为。此外，GJC 功能障碍会影响电导、代谢耦合和第二信使以及炎症反应，这与目前关于 MDD 的假设一致。所有这些结果为 MDD 的神经生物学提供了全面的概述。结论本综述支持以下假设：星形胶质细胞之间 GJC 的调节可能是抗抑郁药治疗效果的潜在机制。
BackgroundMajor depressive disorder (MDD) remains a major public health problem worldwide. The association between MDD and the dysfunction of gap junction channels (GJCs) in glial cells, especially astrocytes, is still controversial.ObjectiveThis review provides an overview of the role of astrocyte GJCs in LMDD.ResultsExposure to chronic unpredictable stress caused a reduction in connexin expression in the rat prefrontal cortex, a result that is consistent with clinical findings reported in postmortem studies of brains from MDD patients. Chronic antidepressant treatment in these rats increased the expression of connexins. However, pharmacological GJC blockade in normal rodents decreased connexin expression and caused depressive-like behaviors. Furthermore, GJC dysfunction affects electrical conductance, metabolic coupling and secondary messengers, and inflammatory responses, which are consistent with current hypotheses on MDD. All these results provide a comprehensive overview of the neurobiology of MDD.ConclusionThis review supports the hypothesis that the regulation of GJCs between astrocytes could be an underlying mechanism for the therapeutic effect of antidepressants.