Gap junction channels as potential targets for the treatment of major depressive disorder

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.