Acupuncture promotes antidepressant effects by enhancing hippocampal neurogenesis via Wnt/β-catenin signaling in a chronic unpredictable mild stress-induced rat depression model.

Abstract

BACKGROUND: Acupuncture is a common complementary treatment for anxiety and depression. This study aimed to investigate whether acupuncture at Shangxing (GV23) and Fengfu (GV16) alleviates chronic unpredictable mild stress (CUMS)-induced depressive-like behaviors in rats, and to explore the underlying mechanisms involving the Wnt/β-catenin signaling pathway. METHOD: Male Sprague-Dawley rats were randomly assigned to five experimental groups: control group (CON), model group (CUMS), fluoxetine group (CUMS + FLX), acupuncture group (CUMS + AP), and sham acupuncture group (CUMS + SAP). Behavioral evaluations of depression-like symptoms were conducted using the sucrose preference test (SPT), open field test (OFT), forced swimming test (FST), and elevated plus maze (EPM). Hippocampal morphology was assessed using hematoxylin-eosin (H&E) and Nissl staining. Ki67 and doublecortin (DCX) expression were detected by immunofluorescence. Western blot (WB) and reverse transcription-polymerase chain reaction (RT-PCR) were conducted to quantify the expression levels of Wnt3a, glycogen synthase kinase 3β (GSK-3β), β-catenin in the hippocampus. RESULT: Our findings indicated that CUMS induced depression-like behaviors, characterized by decreased sucrose preference, reduced locomotion and exploratory activity, less time spent in open arms, and prolonged immobility duration. Furthermore, compared to the CON group, the expression of Wnt3a, Dishevelled-2 (DVL2), β-catenin, the p-GSK-3β to GSK-3β ratio, positive cells of Ki67 and DCX were decreased but GSK-3β was increased in CUMS group. However, the detrimental effects were ameliorated by treatment with fluoxetine and acupuncture. CONCLUSION: Acupuncture at GV23 and GV16 significantly improved depression in CUMS-induced rats by enhancing hippocampal neurogenesis and regulating the Wnt/β-catenin pathway.