Hippocampal expression of Wnt7a and β-catenin in depression: evidence from chronic unpredictable mild stress

This study sought to examine the impact of Wnt7a/β-catenin signaling on depressive-like behaviors by using a rodent model subjected to chronic unpredictable mild stress (CUMS). Hippocampal Wnt7a and β-catenin expression levels were analyzed to investigate their mechanistic involvement in depression. Therefore, 20 male Sprague-Dawley rats were randomly allocated to the control or the CUMS experimental groups. The CUMS group underwent a 30-day stress protocol involving randomized stimuli. This study was authorized by the Ethics Committee (approval no. YXLL2022006). Following model establishment, depression-related behavioral phenotypes were quantitatively evaluated using standardized behavioral paradigms, the sucrose preference test (SPT), and the open field test (OFT), targeting core symptom domains such as anhedonia and alterations in locomotor activity. The morphology of hippocampal CA2 and DG area neurons was examined using hematoxylin and eosin staining, while immunofluorescence and Western blotting assessed Wnt7a and β-catenin expression. Western blotting also assessed GSK-3β and p-GSK-3β expression. Results indicated that CUMS rats showed markedly lower SPT indices (<i>P</i> < 0.05) and decreased OFT parameters (total distance traveled, central zone activity, speed, and central zone duration) <i>versus</i> controls (<i>P</i> < 0.05). Notably, Wnt7a, β-catenin, GSK-3β, and p-GSK-3β were significantly upregulated in the hippocampal tissues of rats in CUMS group (<i>P</i> < 0.05). Collectively, this study found that CUMS-induced depression is associated with a significant upregulation of hippocampal Wnt7a, β-catenin, and GSK-3β, along with increased GSK-3β phosphorylation. This correlative evidence points to Wnt pathway activation in depression pathogenesis and warrants further mechanistic investigation.