Estrogen and the Aging Primate Brain

项目活动包括最近发表的一项研究，在该研究中，我们评估了四种激素疗法(HT)方案对老年手术绝经期恒河猴的认知影响，这些方案旨在模仿女性临床使用的疗法(Baxter等人，2013年)。虽然我们早期的工作已经证明，每月急性注射雌激素有利于老年去卵巢猴子的前额叶皮质调节的工作记忆能力，但在临床研究中，女性的羟色胺往往无法改善认知功能。然而，这种差异反映了HT方案在配方和时间上的差异的可能性尚未得到系统的测试。值得注意的是，在我们的实验中检查的四种激素治疗方法都没有对认知产生任何有益的影响，尽管有文献证明疗效是通过血清激素水平来衡量的。与这些发现一致，并且与我们之前在给予周期雌激素注射的动物的大脑中的结果相反，测试的任何HT方案都没有对猴子前额叶皮质中的树突棘密度产生任何可检测到的影响(Ohm等人，2013年)。该项目的继续工作是测试卵巢激素下降后是否存在保护认知功能的机会之窗，以及与手术更年期和激素治疗对脑形态计量学影响有关的各种相关问题。

Project activities include a recently published study in which we evaluated, in aged surgically menopausal rhesus monkeys, the cognitive effects of four hormone therapy (HT) regimens designed to mimic treatments used clinically in women (Baxter et al., 2013). Whereas our earlier work had demonstrated that monthly acute estrogen injection benefits working memory capacities mediated by the prefrontal cortex in aged ovariectormized monkeys, HT in women has often failed to improve cognitive function in clinical studies. The possibility that this discrepancy reflects differences in the formulation and timing of HT regimens, however, has not been tested systematically. Notably, none of the four hormone treatments examined in our experiments produced any beneficial effects on cognition, despite documented efficacy measured by serum hormone levels. Consistent with these findings, and in contrast to our previous results in brains from animals provided cyclic estrogen administration, none of the HT regimens tested had any detectable effect on dendritic spine density in the monkey prefrontal cortex (Ohm et al., 2013). Continuing work on this project is testing whether there is a window of opportunity for protecting cognitive function after ovarian hormone decline, together with a variety of related questions concerning the brain morphometric influence of surgical menopause and hormone therapy.