Connexin43 and Its Regulation of Astrocyte Gap Junction Function: Influencing Depression Progression by Mediating Electrical and Chemical Signals

CNS Neurosci Ther. 2025 Sep;31(9):e70600. doi: 10.1111/cns.70600.

ABSTRACT

BACKGROUND: Depression is a common mental illness with a high relapse rate, which has a serious negative impact on national economic development and happiness. At present, the pathogenesis of depression is still unclear, and there are inevitable limitations in first-line clinical treatment. Therefore, it is very important to clarify the pathological mechanism of depression for the development of safe and effective antidepressants.

OBJECTIVE: In recent years, considerable research has shown that connexin43 (Cx43) and its regulated astrocyte gap junction (GJ) dysfunction are closely related to the occurrence and development of depression. This review aims to summarize the mechanisms by which Cx43 and its-mediated astrocytic GJs contribute to depression progression, focusing on their regulatory roles in transmitting electrical signals (K⁺, Ca²⁺) and chemical signals (neurotransmitters, inflammatory factors). This work provides theoretical foundations for elucidating the pathological mechanisms of depression and developing novel antidepressant therapies.

CONCLUSION: Cx43 and the gap junctions it regulates in astrocytes play a pivotal role in the pathophysiology of depression by influencing both electrical and chemical signaling between neurons. Further investigation into its mechanisms may offer novel therapeutic approaches for depression.

PMID:40913332 | DOI:10.1111/cns.70600