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Depression has become an important disease threatening human health. In recent years, the efficacy of Traditional Chinese Medicine (TCM) in treating the disease has become increasingly prominent, so it is meaningful to find new antidepressant TCM. Mahonia fortune (Lindl.) Fedde is a primary drug in traditional formulas for the treatment of depression, however, the exact mechanism of its action is unclear. This study aimed to research the effect of MA on the improvement of gap junction function in depression via the miR-205/Cx43 pathway. The antidepressant effects of MA were observed by a rat model of reserpine-induced depression and a model of corticosterone (CORT)-induced astrocytes. The concentrations of neurotransmitters were measured by ELISA, the expression of Connexin 43 (Cx43) protein was measured by Immunohistochemistry, the expression of Cx43, BDNF, CREB proteins were measured by western-blot, the pathological changes of prefrontal cortex were observed by hematoxylin-eosin (H&E) staining. The binding of miR-205 and Cx43 was verified with a Luciferase reporter gene. Gap junction dysfunction detected by fluorescent yellow staining. The results confirmed that MA remarkably decreased miR-205 expression and increased Cx43, BDNF, CREB expression in depression rat and CORT-induced astrocytes. In addition, after overexpression of miR-205 in vitro, MA significantly increased Cx43, BDNF and CREB expression in CORT-induced astrocytes. Thus, MA may target Cx43 through miR-205 to regulate CREB/BDNF signaling pathway to improve depressive behavior. |
