The protective effect of angiotensin II type I receptor blocker (valsartan) on behavioral impairment, NLRP3, BDNF, and oxidative stress in the brain tissue of ovariectomized female rats.

Abstract

Depression and anxiety are common mental health disorders affecting thoughts, behaviors, and emotions. This study aimed to investigate the effect of the angiotensin II type I receptor blocker (AT1RB), valsartan, on menopause-induced depression and anxiety-like behaviors, and to elucidate possible mechanisms of action by measuring levels of nod-like receptor protein 3 (NLRP3), interleukin-1beta (IL-1β), brain-derived neurotrophic factor (BDNF), and oxidative stress in brain tissue. Thirty-two Wistar albino female rats were randomly divided into four groups (n = 8 per group): Control, AT1RB, OVX, and AT1RB + OVX. Following the bilateral ovariectomy (OVX) protocol, physiological saline was used as valsartan solvent, in a maximum volume of 0.4 mL, and valsartan was administered via intragastric gavage at a dose of 40 mg/kg/day. Depression and anxiety-like behaviors were assessed using the forced swimming test and open field test. Levels of oxidative stress markers, NLRP3, IL-1β, BDNF, and CREB were analyzed in the hippocampus and prefrontal cortex tissues. Behavioral tests indicated that depression and anxiety-like behaviors significantly increased in OVX rats (p < 0.01), while AT1RB treatment significantly reduced these behaviors (p < 0.05). In the hippocampus of OVX rats, oxidative stress (p < 0.01), NLRP3 (p < 0.05), and IL-1β (p < 0.01) levels were elevated, whereas BDNF levels were significantly decreased (p < 0.01). AT1RB treatment significantly improved oxidative stress parameters (p < 0.05) and BDNF levels (p < 0.01) but did not significantly affect the increased levels of NLRP3 and IL-1β in OVX rats. In conclusion, AT1RB has a therapeutic effect on menopause-induced depression and anxiety-like behaviors, likely by reducing oxidative stress and increasing BDNF production in the hippocampus.