BIOMARKERS BRAIN PATHOLOGY: RISKS FOR ALZHEIMER?S DISEASE AND DRUG ADDICTION

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 该项目正在开发一种新的更年期模型，以确定为什么女性更容易患阿尔茨海默病，并检查这种疾病的蛋白质生物标志物。 目前，几乎没有生理学相关的更年期动物模型，忠实地模仿人类发生的激素变化。然而，将小鼠暴露于化学物质4-乙烯基环己烯二环氧化物导致卵巢中初级和原始卵泡的损失，导致非常类似于绝经的状态，包括年轻小鼠中可再现的激素和周期性衰老。 转基因小鼠（具有导致老年斑的突变人类基因，如阿尔茨海默氏病）目前正在培育和4-乙烯基环己烯二环氧化物治疗，实验性绝经对APP转基因小鼠A病变发生的影响将使用质谱法进行检查。

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. This venture subproject is developing a novel model of menopause to determine why women are more vulnerable to Alzheimer's disease, and to examine protein biomarkers for this disorder. Presently, there are few physiologically relevant animal models of menopause that faithfully mimic the hormonal changes that occur in humans. However, exposure of mice to the chemical 4-vinylcyclohexene diepoxide results in the loss of primary and primordial follicles in the ovary, resulting in a state that closely resembles menopause, including reproducible hormonal and cyclical senescence in young mice. The transgenic mice (which have a mutant human gene that causes senile plaques like those in Alzheimer's disease) are presently being bred and treated with 4-vinylcyclohexene diepoxide, and the effects of experimental menopause on the genesis of A¿ lesions in ¿APP-transgenic mice will be examined using mass spectrometry.