Estrogen attenuates physical and psychological stress‐induced cognitive impairments in ovariectomized rats

Abstract

Introduction Women are more vulnerable to stress‐related disorders than men, which is counterintuitive as female sex hormones, especially estrogen, have been shown to be protective against stress disorders. Methods In this study, we investigated whether two different models of stress act differently on ovariectomized (OVX) rats and the impact of estrogen on physical or psychological stress‐induced impairments in cognitive‐behaviors. Adult female Wistar rats at 21–22 weeks of age were utilized for this investigation. Sham and OVX rats were subjected to physical and psychological stress for 1 hr/day for 7 days, and cognitive performance was assessed using morris water maze (MWM) and passive avoidance (PA) tests. The open field and elevated plus maze tests (EPM) evaluated exploratory and anxiety‐like behaviors. Results In sham and OVX rats, both physical and psychological stressors were associated with an increase in EPM‐determined anxiety‐like behavior. OVX rats exhibited decreased explorative behavior in comparison with nonstressed sham rats (p < .05). Both physical stress and psychological stress resulted in disrupted spatial cognition as assayed in the MWM (p < .05) and impaired learning and memory as determined by the PA test when the OVX and sham groups were compared with the nonstressed sham group. Estrogen increased explorative behavior, learning and memory (p < .05), and decreased anxiety‐like behavior compared with vehicle in OVX rats exposed to either type of stressor. Conclusions When taken together, estrogen and both stressors had opposite effects on memory, anxiety, and PA performance in a rat model of menopause, which has important implications for potential protective effects of estrogen in postmenopausal women exposed to chronic stress.

Testosterone and estradiol affect adolescent reinforcement learning

“…In adult women, E 2 may promote verbal memory and fluency ( Hamson, Roes & Galea, 2016 ). In gonadectomized male and female rats, E 2 was found to improve learning and memory even after physiological or psychological stressors ( Hamson, Roes & Galea, 2016 ; Khaleghi et al, 2021 ). Moreover, studies with castrated male rats suggested that learning may be improved by testosterone treatment ( Spritzer et al, 2011 ).…”

Dietary Supplementation With Tinospora cordifolia Improves Anxiety-Type Behavior and Cognitive Impairments in Middle-Aged Acyclic Female Rats

“…Similarly, menstruation, post-partum period, ovarian resection conditions, depression, and anxiety-like behavior are correlated with fluctuating levels of estrogen ( Pinkerton et al, 2010 ). A recent study reported acceleration in anxiety-like behavior in ovariectomized rats on their exposure to additional physical and psychological stressors, which was ameliorated with 17 β-estradiol treatment ( Khaleghi et al, 2021 ). Another study reported that one-year metformin therapy for ovariectomized rats ameliorated the long-term effects of ovariectomy-induced anxiety-like behavior ( Zakeri et al, 2019 ).…”

Environmental Enrichment and Estrogen Upregulate Beta-Hydroxybutyrate Underlying Functional Improvement

“…Estrogen-deficiency can induce spatial memory impairment, anxious, and depressive behaviors (Lagunas et al, 2010 ; Djiogue et al, 2018 ). Short-term estrogen treatment can address these physical and psychological stress-induced cognitive impairments (Khayum et al, 2020 ; Khaleghi et al, 2021 ), and prolonged regular (involuntary) exercise can improve estrogen levels in various brain regions and motor coordination performance (Rauf et al, 2015 ). Exercise also exerts the similar effects of estrogen in terms of lipid oxidation, fat reduction, and inflammation regulation in OVX mice (Jackson et al, 2011 ; Pighon et al, 2011 ; Gorres-Martens et al, 2018 ; Fuller et al, 2021 ).…”