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.