INTERACTING IMPACT OF ADRENAL AND OVARIAN AGING ON THE CNS

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 这项建议的总体目标是研究肾上腺和卵巢衰老对灵长类动物中枢神经系统（CNS）的相互影响。使用恒河猴作为一个实用的动物模型，我们已经开始测试的假设，衰老相关的衰减脱氢表雄酮（DHEA）释放加剧围绝经期下降雌二醇。我们有证据表明，这种肾上腺类固醇可以作为中枢神经系统中雌二醇合成的前体，因此它可能有助于维持年轻人健康的脑功能，而其与年龄相关的衰减可能会加剧绝经后发展的神经病理学。我们已经训练动物进行非侵入性认知测试，我们目前正在评估他们的表现后，膳食补充DHEA。到目前为止，结果表明，只要在围绝经期-更年期过渡期早期开始补充DHEA，就可能具有治疗价值。这些研究还研究了肾上腺类固醇如何影响睡眠-觉醒周期的影响，这有助于有效的认知表现。通过阐明卵巢和肾上腺类固醇下降对CNS功能的相互影响，我们希望为开发许多女性衰老相关疾病的治疗方法奠定基础，如认知，学习和注意力，以及昼夜睡眠-觉醒周期的扰动。

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.