Women who undergo bilateral oophorectomy before menopause have increased risk of developing cognitive impairment and dementia than age-matched women, with greater risk the younger the age at oophorectomy (Rocca et al. 2007). Animal models of oophorectomy reveal similar cognitive impairment (Gibbs & Johnson, 2008). The renin angiotensin system (RAS) modulates learning and memory and contributes to the cardiovascular and neuronal protective effects of aerobic exercise. This project focuses on the role of key mediators of the RAS, i.e., angiotensin II receptors (AT1R & AT2R) in mechanisms of cognitive impairment induced by ovariectomy and the cognitive protective effects of aerobic exercise in normotensive and hypertensive rats to differentiate blood pressure-dependent and -independent effects of AT1R & AT2R actions with two specific aims:
Our proposal addresses the important societal issue of cognitive decline with aging and neurodegenerative disease, with a primary focus on Alzheimer's dementia. The special relevance of our study is: 1) Our studies focus on females; 2) They model an understudied group of women at increased risk of cognitive loss due to premenopausal removal of the ovaries; 3) We bring expertise in the brain RAS and blood pressure regulation that is implicated in cognition and neuronal protective effects of aerobic exercise albeit understudied in mechanisms of cognitive impairment and Alzheimer's disease; and, 4) We are focusing on a non-pharmacological as well as pharmacological interventions for cognitive protection - namely, aerobic exercise and RAS inhibition, which have not been studied in ovariectomy-induced cognitive impairment.