State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical, Science and Peking Union Medical College, Beijing 100050, China.
Department of Anatomy, School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China.
Molecules. 2023 Feb 15;28(4):1820. doi: 10.3390/molecules28041820.
Major depressive disorder (MDD) is a leading chronic mental illness worldwide, characterized by anhedonia, pessimism and even suicidal thoughts. Connexin 43 (Cx43), mainly distributed in astrocytes of the brain, is by far the most widely and ubiquitously expressed connexin in almost all vital organs. Cx43 forms gap junction channels in the brain, which mediate energy exchange and effectively maintain physiological homeostasis. Increasing evidence suggests the crucial role of Cx43 in the pathogenesis of MDD. Neuroinflammation is one of the most common pathological features of the central nervous system dysfunctions. Inflammatory factors are abnormally elevated in patients with depression and are closely related to nearly all links of depression. After activating the inflammatory pathway in the brain, the release and uptake of glutamate and adenosine triphosphate, through Cx43 in the synaptic cleft, would be affected. In this review, we have summarized the association between Cx43 and neuroinflammation, the cornerstones linking inflammation and depression, and Cx43 abnormalities in depression. We also discuss the significant association of Cx43 in inflammation and depression, which will help to explore new antidepressant drug targets.
重度抑郁症（MDD）是一种全球范围内主要的慢性精神疾病，其特征为快感缺失、悲观甚至自杀念头。间隙连接蛋白 43（Cx43）主要分布在大脑的星形胶质细胞中，是迄今为止在几乎所有重要器官中表达最广泛和最普遍的连接蛋白。Cx43 在大脑中形成间隙连接通道，介导能量交换并有效维持生理内稳态。越来越多的证据表明 Cx43 在 MDD 的发病机制中起着关键作用。神经炎症是中枢神经系统功能障碍的最常见病理特征之一。抑郁症患者的炎症因子异常升高，与抑郁症的几乎所有环节都密切相关。在大脑中激活炎症途径后，谷氨酸和三磷酸腺苷的释放和摄取会通过突触间隙中的 Cx43 受到影响。在这篇综述中，我们总结了 Cx43 与神经炎症之间的关联，以及连接炎症和抑郁症的基石，以及抑郁症中 Cx43 的异常。我们还讨论了 Cx43 在炎症和抑郁症中的重要关联，这将有助于探索新的抗抑郁药物靶点。
