Women are at an increased risk for cognitive decline after natural or surgical menopause due to the permanent loss of ovarian hormones. Hormone replacement therapy, which is typically prescribed for climacteric symptoms associated with menopause, can also provide some cognitive benefits. However, the adverse side effects of long-term treatment prevent its prolonged use. Few investigations to date have looked at the long-term impact of hormone replacement after treatment has been discontinued. We have developed a middle-aged rodent model of short-term estrogen replacement therapy which is as effective as long-term, continuous treatment at improving spatial working memory. It also induces sustained upregulation of its cognate alpha- receptor, in the hippocampus, a region of the brain required for spatial working memory. While hippocampal function can benefit from estrogen treatment, other cognitive domains may be adversely affected or remain unaffected. Thus, we propose to examine the utility of our model in protecting prefrontal cortical function, which is particularly susceptible to deterioration during advanced aging and can be unaffected or worse, impaired, by prolonged estrogen exposure. Given that estrogen therapy can have opposing effects in a brain region-specific manner and the risks associated with extended use, it is imperative that we develop adjuvant or alternative therapeutic strategies. Aerobic exercise is an obvious candidate because it has general health and cognitive benefits, is neuroprotective during aging, and is a cost-free nonpharmacological intervention. Our main objective, therefore, is to demonstrate the capacity for these two therapies to be used in combination to promote healthy aging post menopause. We expect combination therapy to be maximally beneficial for physiological and brain health. Moreover, evaluating the effects of the two strategies on brain plasticity, alone and in combination, will provide valuable insight into the divergence and overlap in their underlying mechanisms of action.

Public Health Relevance

Public Health Significance: Results from this project will elucidate the interactive effects of exercise and short- term, transient estrogen exposure on multiple aspects of cognitive function and the underlying neurobiological mechanisms. Such knowledge will inform the development of improved postmenopausal treatment strategies to protect against cognitive decline in aging women.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AG056039-01
Application #
9298789
Study Section
Biobehavioral Regulation, Learning and Ethology Study Section (BRLE)
Program Officer
Roberts, Luci
Project Start
2017-09-15
Project End
2019-05-31
Budget Start
2017-09-15
Budget End
2018-05-31
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Houston
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
036837920
City
Houston
State
TX
Country
United States
Zip Code
77204