SELECTIVE ESTROGEN RECEPTOR MODULATORS AND COGNITION

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。雌二醇（E2）替代疗法（ERT）用于雌激素水平低下的女性，以预防骨质疏松症、心血管疾病、性功能障碍、情绪障碍和与卵巢切除术或更年期相关的认知障碍。然而，ERT会增加患乳腺癌或子宫癌的风险。选择性雌激素受体调节剂（SERMs）已被开发来解决这些问题。serm模拟雌激素对特定组织的积极作用，但对乳房和子宫内膜的增殖作用最小。然而，SERMS对认知的影响尚不清楚。我们使用恒河猴模型来确定SERMs他莫昔芬和雷洛昔芬对认知功能的影响。对动物进行一系列计算机化的记忆和注意力测试，这些测试对性激素或卵巢状态很敏感，包括延迟不匹配样本、延迟识别广度和视觉搜索测试。由于认知表现会受到运动能力的影响，我们扩大了这个项目的范围，包括对运动行为的评估。在最初的一个项目中，我们训练去卵巢和性腺完整的猴子从一个有机玻璃板上提取葡萄干，这样获得葡萄干的最佳方法是用双手协调地使用。结果表明，卵巢状态对这项任务没有影响，两组的表现都随着时间的推移而有所改善。我们正在继续研究卵巢切除术和激素治疗对运动功能以及更复杂的认知任务的影响。此外，我们还研究了正常女性的月经周期是否会影响静息脑活动，这是通过PET成像程序来评估葡萄糖代谢的。结果表明，与焦虑调节有关的几个区域在整个周期中表现出变化。进一步的研究将检验激素治疗对从事认知任务的猴子脑葡萄糖代谢的影响。

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. Estradiol (E2) replacement therapy (ERT) is prescribed to hypoestrogenic women to protect against osteoporosis, cardiovascular disease, sexual dysfunction, mood disorders and cognitive impairments associated with ovariectomy or menopause. However, ERT increases risk of developing breast or uterine cancer. Selective estrogen receptor modulators (SERMs) have been developed to address these problems. SERMs mimic the positive effects of estrogens on specific tissues, yet have minimal proliferative effects on breast and endometrium. The effects of SERMS on cognition, however, are not known. We use the rhesus monkey model to determine the effects of the SERMs tamoxifen and raloxifene on cognitive function. Animals are tested on a battery of computerized memory and attentional tests that are sensitive to sex hormones or ovarian status, including Delayed Non-Matching to Sample, Delayed Recognition Span, and Visual Search tests. Because cognitive performance can be affected by motor ability, we expanded the scope of this project to include assessments of motor behavior. In an initial project we trained ovariectomized and gonadally intact monkeys to extract raisins from a Plexiglas board designed so that the optimal method of obtaining the raisins was to use both hands in a coordinated manner. Results indicated that ovarian status was without effect upon this task with both groups showing improvements in performance over time. We are continuing to study the influence of ovariectomy and hormonal treatments on motor function as well as upon the more complex battery of cognitive tasks. In addition, we have examined whether menstrual cyclicity in normal females influences resting brain activity as indicated by a PET imaging procedure that assesses glucose metabolism. Results indicate that several areas involved in the regulation of anxiety show changes across the cycle. Further studies will examine the effects of hormonal treatments on brain glucose metabolism in monkeys engaged in cognitive tasks.