rTMS ameliorates CUMS-induced anxiety-depression-like behaviour and cognitive dysfunction in rats by modulating the COX-2/PGE2 signalling pathway

Abstract

BACKGROUND: rTMS is a safe and effective neuromodulation method for treating depression, but the specifics of its antidepressant effects and the underlying mechanisms remain uncertain. METHODS: Male SD rats were randomly divided into four groups: control group, CUMS group, CUMS + rTMS (10 Hz) group, and CUMS + celecoxib (25 mg/kg, as a positive control) group. Depression-like behavior was assessed by weight change, SPT, and FST; anxiety by OFT and EPM; and cognitive function by the Y-maze. WB, IF, ELISA, and qPCR were used to observe changes in COX-2/PGE2 signaling pathway-related proteins, inflammatory factors, and the activation of astrocytes and microglia in the hippocampus of rats. RESULTS: Compared to the control group, rats in the CUMS group exhibited significant anxiety-depression-like behavior and cognitive dysfunction. Compared to the CUMS group, rTMS and celecoxib interventions improved anxiety-depression-like behavior and cognitive dysfunction, reduced the expression of microglia and astrocytes, reversed the upregulation of pro-inflammatory factors (IL-1β, IL-6, TNF-α), and downregulated the expression of proteins related to the COX-2/PGE2 signaling pathway in CUMS-induced rats. CONCLUSIONS: The study demonstrated that rTMS could improve anxiety-depression-like behavior and cognitive dysfunction in rats by modulating the COX-2/PGE2 pathway.