Effects of dietary phytoestrogens on the aging brain

本提案的总体目标是研究膳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。围绝经期妇女被鼓励增加植物雌激素（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，但对它们可能对中枢神经系统产生的影响知之甚少。内源性和合成雌激素已被发现影响脑形态（如树突脊柱密度）和基因转录（如雌激素受体mRNA），提供对缺血性事件脑损伤的抵抗力，并增强认知能力。植物雌激素结合雌激素受体（erα和erβ），

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.