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

cell-biology
neurology
psychiatry-and-psychology
mental-health

Abstract

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 in 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 — sucrose preference test (SPT) and 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 (P<0.05) and decreased OFT parameters (total distance traveled, central zone activity, speed, central zone duration) versus controls (P<0.05). Notably, Wnt7a, β-catenin, GSK-3β, and p-GSK-3β were significantly upregulated in the hippocampal tissues of rats in CUMS group (P<0.05). Collectively, this study demonstrated that CUMS-induced depression triggered significant upregulation of hippocampal Wnt7a, β-catenin, GSK-3β, and significant increase in GSK-3β phosphorylation implying Wnt pathway activation may contribute to depression pathogenesis.
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