Effects of dietary phytoestrogens on the aging brain

这项建议的总体目标是调查饮食水平的植物雌激素对衰老的中枢神经系统(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(在大豆中发现)的摄入量，作为合成激素替代疗法的替代方案。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，但人们对它们可能对中枢神经系统产生的影响知之甚少。已发现内源性和合成雌激素影响脑形态(如树突棘密度)和基因转录(如雌激素受体mRNA)，提供对缺血事件造成的脑损伤的抵抗，并提高认知能力。植物雌激素与雌激素受体(ERα和ERβ)结合， 在饮食水平上，可能具有类似于中枢神经系统17β雌二醇(E2)的神经保护作用。对于这一提议，植物雌激素对涉及认知功能的大脑区域的影响尤其令人感兴趣。 利用老化的啮齿动物模型，将在小型、独立的研究项目中解决两个具体目标： 1)评估饮食中植物雌激素的认知效应；2)评估饮食中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。对于具体目标1，终点包括获得和执行记忆密集型任务，以及在摄入含有或不含有植物雌激素的大豆蛋白制成的饮食后的神经解剖和神经化学措施。对于特定的目标2，终点包括形态测量(梗死灶的大小)和梗死灶周围有缺血损伤的细胞的数量。

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.