INTERACTING IMPACT OF ADRENAL AND OVARIAN AGING ON THE CNS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 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。使用雌性恒河猴作为一个务实的动物模型，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。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. 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 the female rhesus macaque 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. 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.