Losartan attenuates depression-like behavior in epileptic rats by regulating the TGF-β/Smad signaling.

OBJECTIVE: This study aims to investigate the role of the TGF-β/Smad Signaling in depression comorbidity in epileptic individuals and to evaluate the effect of losartan on depressive symptoms. METHODS: Li-Popilocarpine was used to induce status epilepticus (SE) in rats. The rats in which SE was successfully induced were randomly divided into the SE saline group and the SE losartan group. Then, the rats in the different groups were given the corresponding interventions for 20 days. After the intervention, the depression levels of the rats in each group were evaluated. Upon completion of the intervention, brain tissue was collected for comprehensive assessment of TGF-β mRNA levels, TGF-β/Smad Signaling-related protein expression, and GFAP⁺ astrocyte density in the rat hippocampus. RESULTS: The depression-like behavior of SE rats was more obvious than that of control rats. TGF-β mRNA, p-Smad2, p-Smad3 and GFAP⁺ astrocyte expression levels were significantly greater in SE rats than in control rats. Compared with the SE-saline group, the depression-like behavior of the SE-losartan group improved. The expression levels of TGF-β mRNA p-Smad2, p-Smad3 and GFAP⁺ astrocyte expression in the SE-losartan group rats were lower than those in the SE-saline group. CONCLUSION: The TGF-β/Smad Signaling is an important Signaling leading to depression-like behavior in epileptic rats. Losartan is a drug that can significantly improve the depression-like behavior of epileptic rats by regulating the TGF-β/Smad Signaling. Findings in this study support losartan as a repurposable central nervous system drug for comorbid depression in epilepsy, warranting further clinical investigation.