Laboratoire de Physiologie Humaine, Faculte de Medecine et Pharmacie, Universite de Poitiers, 6 rue de la Miletrie, Bat D1, TSA 51115, 86073 Poitiers, Cedex 9, France.
STIM, ERL 7003, CNRS-Universite de Poitiers, Pole Biologie Sante, Bat B36, TSA 51106, 1 rue Georges Bonnet, 86073 Poitiers, Cedex 9, France.
Curr Med Chem. 2019;26(20):3775-3791. doi: 10.2174/0929867325666180327103530.
Major depressive disorder (MDD) is a multifactorial chronic and debilitating mood disease with high lifetime prevalence and associated with excess mortality. Treatments for this disease are not effective in all patients showing the need to find new therapeutic targets.
This review aims to update our knowledge on the involvement of astroglial gap junctions and hemichannels in MDD and to show how they have become potential targets for the treatment of this pathology.
The method applied in this review includes a systematic compilation of the relevant literature.
The use of rodent models of depression, gene analysis of hippocampal tissues of MDD patients and post-mortem studies on the brains from MDD patients suggest that astrocytic gap junction dysfunction may be a part of MDD etiologies. Chronic antidepressant treatments of rats, rat cultured cortical astrocytes and human astrocytoma cell lines support the hypothesis that the up-regulation of gap junctional coupling between astrocytes could be an underlying mechanism for the therapeutic effect of antidepressants. However, two recent functional studies suggest that connexin43 hemichannel activity is a part of several antidepressants' mode of action and that astrocyte gap junctional intercellular communication and hemichannels exert different effects on antidepressant drug response. Even if they emerge as new therapeutic targets for new and more active treatments, further studies are needed to decipher the sophisticated and respective role of astrocytic gap junctions and hemichannels in MDD.
重度抑郁症（MDD）是一种多因素的慢性、使人虚弱的情绪疾病，终生患病率高，且与死亡率升高有关。并非所有患者对该病的治疗都有效，这表明需要寻找新的治疗靶点。
本篇综述旨在更新我们对星形胶质细胞缝隙连接和半通道在 MDD 中作用的认识，并展示它们如何成为该病理治疗的潜在靶点。
本综述应用的方法包括系统地汇编相关文献。
使用抑郁模型动物、MDD 患者海马组织的基因分析以及 MDD 患者死后大脑的研究表明，星形胶质细胞缝隙连接功能障碍可能是 MDD 病因的一部分。慢性抗抑郁治疗的大鼠、大鼠培养皮质星形胶质细胞和人星形胶质细胞瘤细胞系支持这样的假说，即星形胶质细胞之间缝隙连接偶联的上调可能是抗抑郁药治疗效果的潜在机制。然而，最近的两项功能研究表明，连接蛋白 43 半通道活性是几种抗抑郁药作用模式的一部分，星形胶质细胞缝隙连接细胞间通讯和半通道对抗抑郁药物反应有不同的影响。即使它们成为新的和更有效的治疗方法的新治疗靶点，仍需要进一步研究来阐明星形胶质细胞缝隙连接和半通道在 MDD 中的复杂和各自的作用。
