Discriminating sex chromosome and hormonal effects on brain sexual dimorphisms

项目摘要/摘要 男性和女性表现出不同的神经和精神疾病的发病率和模式 疾病，这表明一种性别可能拥有更高水平的因素来保护 疾病，或较低水平的加剧疾病的因素。中国的长期目标是 该项目旨在确定大脑的哪些区域会受到性别偏见因素的影响，例如 性染色体编码的基因和性腺激素水平 成人期。因为这些类型的性别偏见保护是由不同的 分子机制，区分每个因子的作用部位是第一步 了解性别偏见保护是如何运作的。拟议的研究 使用全脑磁共振成像来测量每个大脑的大小 地区，在特定性别偏见因素可能严格存在的条件下 被操纵以观察它们各自的影响。性染色体非整倍体的大脑 而野生型(XO、XX、XY和XXY)将在小鼠有或没有有 他们的性腺。实验设计将决定哪些性别在体积上的差异 大脑区域的数量受到X染色体的数量和存在的影响 Y染色体的缺失以及睾丸和卵巢分泌物的水平 成人期。结果将建立大脑区域和局部功能 受不同性别偏见机制的影响。结果将改变概念上的 研究受影响的脑区保护机制的框架 神经和精神疾病。

Project Summary / Abstract Men and women show different incidence and patterns of neurological and psychiatric diseases, indicating that one sex may possess higher levels of factors that protect from disease, or lower levels of factors that exacerbate disease. The long-term goal of the project is to determine which brain regions are influenced by sex-biasing factors such as the genes encoded by the sex chromosomes and the level of gonadal hormones in adulthood. Because these types of sex-biased protection are mediated by different molecular mechanisms, discriminating the sites of action of each factor is the first step towards understanding how sex-biased protection operates. The proposed research involves whole-brain magnetic resonance imaging to measure the size of every brain region, under conditions in which specific sex-biasing factors can be rigorously manipulated to observe their individual effects. The brains of sex chromosome aneuploid and wild-type (XO, XX, XY and XXY) will be compared when mice have or do not have their gonads. The experimental design will determine which sex differences in volumes of brain regions are influenced by the number of X chromosomes, and by the presence / absence of the Y chromosome, and by the levels of testicular and ovarian secretions in adulthood. The results will establish the brain regions and localized functions that are influenced by different sex-biasing mechanisms. The outcome will alter conceptual frameworks for investigating protective mechanisms in brain regions affected by neurological and psychiatric disease.