State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
College of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China.
Psychopharmacology (Berl). 2018 Jan;235(1):1-12. doi: 10.1007/s00213-017-4782-7. Epub 2017 Nov 25.
Major 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.
This review provides an overview of the role of astrocyte GJCs in LMDD.
Exposure 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.
This review supports the hypothesis that the regulation of GJCs between astrocytes could be an underlying mechanism for the therapeutic effect of antidepressants.
重度抑郁症（MDD）仍然是全球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）中缝隙连接通道（GJCs）功能障碍之间的关联仍存在争议。
本文综述了星形胶质细胞 GJCs 在 LMDD 中的作用。
慢性不可预测应激暴露导致大鼠前额叶皮质中连接蛋白表达减少，这与 MDD 患者尸检研究报告的临床发现一致。在这些大鼠中，慢性抗抑郁治疗增加了连接蛋白的表达。然而，在正常啮齿动物中，药理学 GJC 阻断会降低连接蛋白的表达并引起类似抑郁的行为。此外，GJC 功能障碍会影响电导率、代谢偶联和第二信使以及炎症反应，这与 MDD 的当前假说一致。所有这些结果为 MDD 的神经生物学提供了全面的概述。
本综述支持这样一种假设，即星形胶质细胞之间 GJCs 的调节可能是抗抑郁药治疗效果的潜在机制。
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