INTERACTING IMPACT OF ADRENAL AND OVARIAN AGING ON THE CNS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项建议的总体目标是研究肾上腺和卵巢老化对灵长类动物中枢神经系统(CNS)的交互影响。使用恒河猴作为一个实用的动物模型，我们已经开始检验与衰老有关的假设 脱氢表雄酮(DHEA)释放的减少加剧了围绝经期雌二醇的下降。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雌二醇合成的前体，因此它可能有助于维持年轻人的健康大脑功能，它的衰老相关的衰减可能会加剧绝经后发生的神经病理。我们已经训练动物进行非侵入性认知测试，目前我们正在评估它们在饮食补充DHEA后的表现。这些研究还在研究肾上腺类固醇如何影响睡眠-觉醒周期，这可能有助于有效的认知表现。通过阐明卵巢和肾上腺类固醇激素下降对中枢神经系统功能的交互影响，我们期望为开发治疗女性许多与衰老相关的疾病，如认知、学习和注意力，以及扰乱昼夜睡眠-觉醒周期奠定基础。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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. 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.