Effects of dietary phytoestrogens on the aging brain

本提案的总体目标是调查膳食植物雌激素水平对衰老中枢神经系统（CNS）具有神经保护作用的假设。鼓励围绝经期妇女增加植物雌激素（大豆中发现）的摄入量，作为合成激素替代疗法的替代品。有证据表明，植物雌激素可以预防骨质疏松症和心血管疾病，但对它们可能具有的中枢神经系统作用知之甚少。已经发现内源性和合成雌激素影响脑形态（例如，树突棘密度）和基因转录（例如，雌激素受体mRNA），提供对缺血性事件引起的脑损伤的抵抗力，并增强认知能力。植物雌激素结合雌激素受体（ER α和ER β）， 在饮食水平下，可能具有类似于17 β雌二醇（E2）对CNS的神经保护作用。对于这个提议，植物雌激素对参与认知功能的大脑区域的影响特别令人感兴趣。 使用老化啮齿动物模型，将在小型独立研究项目中解决2个具体目标： 1)评价膳食植物雌激素的认知作用; 2）评价膳食植物雌激素在缺血性中风啮齿动物模型中的神经保护作用。对于特定目标1，终点包括记忆密集型任务的获得和执行，以及摄入含有或不含植物雌激素的大豆蛋白饮食后的神经解剖学和神经化学测量。对于特定目标2，终点包括形态学测量（梗死面积）和梗死周围区域中缺血诱导损伤的细胞数量。

The overall objective of this proposal is to investigate the hypothesis that dietary levels of phytoestrogens are neuroprotective to the aging central nervous system (CNS). Perimenopausal women are encouraged to increase their intake of phytoestrogens (found in soy) as an alternative to synthetic hormone replacement therapy. Evidence suggests that phytoestrogens can protect against osteoporosis and cardiovascular disease, but little is known about what CNS effects they may have. Endogenous and synthetic estrogens have been found to affect brain morphology (e.g., dendritic spine density) and gene transcription (e.g., estrogen receptor mRNA), provide resistance to brain damage from ischemic events, and enhance cognitive performance. Phytoestrogens bind the estrogen receptors (ERalpha and ERbeta), and at dietary levels may have neuroprotective actions similar to 17beta estradiol (E2) on the CNS. For this proposal, effects of phytoestrogens on brain regions involved in cognitive function are of particular interest. Using an aging rodent model, 2 specific aims will be addressed in small, self-contained research projects: 1) assessment of cognitive effects of dietary phytoestrogens; 2) assessment of the neuroprotective role of dietary phytoestrogens in a rodent model of ischemic stroke. For specific aim 1, end points include acquisition and performance of memory-intensive tasks, as well as neuroanatomical and neurochemical measures after intake of diets made of soy protein with or without phytoestrogens. For specific aim 2, end points include morphological measures (size of infarct) and number of cells with ischemia-induced damage in regions surrounding the infarct.