Estrogen and the Aging Primate Brain

这一多机构合作项目的进展主要集中在行为特征受试者大脑中与雌激素状态有关的定量形态计量分析。例如，在最近发表的一项研究中，Hara和他的同事测试了恒河猴在衰老过程中前额叶皮质线粒体的形态和数量是否发生了变化。值得注意的是，雌激素治疗逆转了在卵巢切除女性中观察到的行为缺陷和与年龄相关的线粒体形状变化。这些发现与激素替代部分通过影响线粒体功能，进而影响突触完整性，从而改善衰老的认知结果的观点一致。这一结果补充了该模型最近发表的其他证据，这些证据表明，与我们早先报道的周期雌激素治疗的行为和突触效应相反，女性临床实践中采用的多种激素治疗方案未能改善认知功能或前额叶皮质中树突棘的密度。总体而言，该项目继续澄清一些重要的问题，涉及卵巢激素对正常认知老化的调节影响。

Progress on this multi-institutional collaborative project has focused primarily on quantitative morphometric analysis in the brains of behaviorally characterized subjects in relation to estrogen status. In a recently published study, for example, Hara and colleagues tested whether mitochondria morphology and number are altered in the prefrontal cortex during aging in rhesus monkeys. Notably, estrogen treatment reversed both the behavioral deficits and aged-related changes in mitochondria shape observed in ovariectomized females. These findings are consistent with the idea that hormone replacement benefits the cognitive outcome of aging partly through influencing mitochondrial function, with downstream effects on synaptic integrity. The results complement other recently published evidence from this model demonstrating that, in contrast to the behavioral and synaptic effects of cyclic estrogen treatment we reported earlier, multiple hormone therapy regimens adapted from clinical practice in women fail to improve cognitive function or dendritic spine density in the prefrontal cortex. Overall this project continues to clarify a number of significant issues concerning the modulatory influence of ovarian hormones on normal cognitive aging.