SELECTIVE ESTROGEN RECEPTOR MODULATORS AND COGNITION

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。雌激素(E2)替代疗法(ERT)被开给雌激素分泌不足的妇女，以预防骨质疏松、心血管疾病、性功能障碍、情绪障碍和与卵巢切除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(SERM)就是为了解决这些问题而开发的。SERM模拟雌激素对特定组织的积极作用，但对乳腺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SERM三苯氧胺和雷洛昔芬对认知功能的影响。对动物进行了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况很敏感，包括延迟与样本匹配、延迟识别持续时间和视觉搜索测试。因为认知能力可能会受到运动能力的影响，所以我们扩大了这个项目的范围，将运动行为的评估包括在内。在最初的项目中，我们训练卵巢切除和性腺完整的猴子从有机玻璃板上提取葡萄干，这种设计使得获得葡萄干的最佳方法是协调使用双手。结果表明，卵巢状况对这项任务没有影响，随着时间的推移，两组人的表现都有所改善。我们正在继续研究卵巢切除和激素治疗对运动功能的影响，以及对更复杂的认知任务的影响。此外，我们还检查了正常女性的月经周期是否会影响静息状态下的大脑活动，这是由评估葡萄糖代谢的PET成像程序所显示的。结果表明，参与焦虑调节的几个区域在整个周期中都会发生变化。进一步的研究将检验激素治疗对参与认知任务的猴子大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.