Effects of coumestrol on oxidative, apoptotic and cognitive factors of male mice in chronic restraint stress model

Abstract

Background: Coumestrol (COUM) is well-known as a natural estrogen receptor-beta (ERβ) modulator. The role of estrogen receptors in controlling stressful situations has already been reported and their cognitive functions in the hippocampus seem to be similar in both genders and independent of sexual tasks. Aim: The aim of this study was to investigate the improving effects of this phytoestrogen on the negative consequences of exposing male mice to chronic restraint stress. Methods: This study was divided into two separate but consecutive phases. In the first phase, the possible effects of COUM (30, 60, 120 µg.kg-1.day-1, i.p.) and its vehicle (sesame oil) on restraint stress-induced cognitive impairments, oxidative stress and apoptosis were evaluated. During the second phase, a selective ERβ antagonist was used to investigate the possible involvement of ERβs in these processes. Morris water maze (MWM) and novel object recognition (NOR) tests were performed to evaluate memory while elevated plus maze (EPM) test was used to measure the level of anxiety. Spectroscopy and western blotting methods were also employed to evaluate oxidative and apoptotic status in hippocampal tissue. Furthermore, serum level of corticosterone (CORT) was measured for each group. Results: Behavioral tests indicated memory enhancing and anxiolytic effects of COUM. Biochemical evaluations also proved its antioxidant and anti-apoptotic potential. On the other hand, the mentioned behavioral and biochemical improvements were reversed in ERβ antagonist-treated group. Conclusion: COUM may ameliorate negative consequences of exposure to chronic stress such as oxidative stress, apoptosis and cognitive impairments, via the modulation of hippocampal ERβs.