INTERACTING IMPACT OF ADRENAL AND OVARIAN AGING ON THE CNS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The overall aim of this proposal is to examine the interacting impact of adrenal and ovarian aging on the central nervous system (CNS) of primates. Using rhesus macaques as a pragmatic animal model, we have begun to test the hypothesis that aging-related attenuation of dehydroepiandrosterone (DHEA) release exacerbates the perimenopausal decline in estradiol. We have evidence that this adrenal steroid can act as a precursor for estradiol synthesis in the CNS, and so it is likely to contribute to the maintenance of healthy brain function in the young, and its aging-related attenuation may exacerbate the neuropathologies that develop after menopause. We have trained animals to perform noninvasive cognitive tests and we are currently evaluating their performance after dietary supplementation with DHEA. So far the results suggest that DHEA supplementation may have therapeutic value, as long as it is initiated early during the perimenopause-menopause transition period. The studies are also examining the impact of how adrenal steroids affect sleep-wake cycles, which can contribute to effective cognitive performance. By elucidating the interacting impact of declining ovarian and adrenal steroids on CNS function, we expect to lay a foundation for the development of therapies for many aging-associated disorders in women, such as cognition, learning, and attention, as well as perturbations of the circadian sleep-wake cycle.