Astroglial Connexin 43-Mediated Gap Junctions and Hemichannels: Potential Antidepressant Mechanisms and the Link to Neuroinflammation.

IF 3.6 4区 医学 Q3 CELL BIOLOGY
Cellular and Molecular Neurobiology Pub Date : 2023-11-01 Epub Date: 2023-10-24 DOI:10.1007/s10571-023-01426-5
Lan Lei, Ya-Ting Wang, Die Hu, Cong Gai, Yi Zhang
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Abstract

Major depression disorder (MDD) is a neuropsychiatric disorder associated with a high suicide rate and a higher disability rate than any other disease. Evidence suggests that the pathological mechanism of MDD is related to astrocyte dysfunction. Depression is mainly associated with the expression of connexin 43 (Cx43) and the function of Cx43-mediated gap junctions and hemichannels in astrocytes. Moreover, neuroinflammation has been a hotspot in research on the pathology of depression, and Cx43-mediated functions are thought to be involved in neuroinflammation-related depression. However, the specific mechanism of Cx43-mediated functions in neuroinflammation-related depression pathology remains unclear. Therefore, this review summarizes and discusses Cx43 expression, the role of gap junction intercellular communication, and its relationship with neuroinflammation in depression. This review also focuses on the effects of antidepressant drugs (e.g., monoamine antidepressants, psychotropic drugs, and N-methyl-D-aspartate receptor antagonists) on Cx43-mediated function and provides evidence for Cx43 as a novel target for the treatment of MDD. The pathogenesis of MDD is related to astrocyte dysfunction, with reduced Cx43 expression, GJ dysfunction, decreased GJIC and reduced BDNF expression in the depressed brain. The effect of Cx43 on neuroinflammation-related depression involving inflammatory cytokines, glutamate excitotoxicity, and HPA axis dysregulation. Antidepressant drugs targeting Cx43 can effectively relieve depressive symptoms.

Abstract Image

星形胶质连接蛋白43介导的间隙连接和半通道:潜在的抗抑郁机制和与神经炎症的联系。
重度抑郁症(MDD)是一种与高自杀率和比任何其他疾病更高的残疾率相关的神经精神障碍。有证据表明MDD的病理机制与星形胶质细胞功能障碍有关。抑制主要与星形胶质细胞中连接蛋白43(Cx43)的表达以及Cx43介导的间隙连接和半通道的功能有关。此外,神经炎症一直是抑郁症病理学研究的热点,Cx43介导的功能被认为与神经炎症相关的抑郁症有关。然而,Cx43介导的功能在神经炎症相关的抑郁症病理中的具体机制尚不清楚。因此,本文综述并讨论了Cx43在抑郁症中的表达、间隙连接细胞间通讯的作用及其与神经炎症的关系。这篇综述还集中于抗抑郁药物(如单胺类抗抑郁药、精神药物和N-甲基-D-天冬氨酸受体拮抗剂)对Cx43介导的功能的影响,并为Cx43作为治疗MDD的新靶点提供了证据。MDD的发病机制与星形胶质细胞功能障碍有关,在抑郁的大脑中,Cx43表达减少、GJ功能障碍、GJIC降低和BDNF表达减少。Cx43对神经炎症相关抑郁的影响,包括炎性细胞因子、谷氨酸兴奋性毒性和HPA轴失调。针对Cx43的抗抑郁药物可以有效缓解抑郁症状。
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来源期刊
CiteScore
7.70
自引率
0.00%
发文量
137
审稿时长
4-8 weeks
期刊介绍: Cellular and Molecular Neurobiology publishes original research concerned with the analysis of neuronal and brain function at the cellular and subcellular levels. The journal offers timely, peer-reviewed articles that describe anatomic, genetic, physiologic, pharmacologic, and biochemical approaches to the study of neuronal function and the analysis of elementary mechanisms. Studies are presented on isolated mammalian tissues and intact animals, with investigations aimed at the molecular mechanisms or neuronal responses at the level of single cells. Cellular and Molecular Neurobiology also presents studies of the effects of neurons on other organ systems, such as analysis of the electrical or biochemical response to neurotransmitters or neurohormones on smooth muscle or gland cells.
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