Discriminating sex chromosome and hormonal effects on brain sexual dimorphisms

区分性染色体和激素对大脑性别二态性的影响

• 批准号: 9376919
• 负责人: Arthur P Arnold
• 金额: $ 23.28万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9376919
• 关键词: Adult; Affect; Anatomy; Aneuploidy; Area; Atlases; Brain; Brain region; Cell Size; Cells; Cerebellar cortex structure; Cerebral cortex; Chromosomes; Collaborations; Corpus Callosum; Development; Disease; Experimental Designs; Female; Fimbria of hippocampus; Foundations; Genes; Genotype; Goals; Gonadal Hormones; Gonadal Steroid Hormones; Gonadal structure; Hormonal; Hormones; Image Analysis; Incidence; Individual; Inequality; Lead; Magnetic Resonance Imaging; Measurement; Measures; Mediating; Mental disorders; Modeling; Modernization; Molecular; Mus; Occipital lobe; Outcome; Ovarian; Ovary; Pattern; Phenotype; Population; Reproduction; Research; Safe Sex; Sex Bias; Sex Characteristics; Sex Chromosomes; Site; Structure; Techniques; Testis; Woman; X Chromosome; Y Chromosome; base; brain cell; brain morphology; brain size; brain volume; density; experimental study; gray matter; imaging study; male; men; morphometry; mouse model; multilevel analysis; nervous system disorder; neuroprotection; neuropsychiatric disorder; novel; novel therapeutics; relating to nervous system; sex; sexual dimorphism; theories

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.

项目总结/摘要 男性和女性表现出不同的发病率和模式的神经和精神 疾病，表明一种性别可能拥有更高水平的因素，保护免受 疾病，或降低加剧疾病的因素水平。的长期目标 该项目旨在确定哪些大脑区域受到性别偏见因素的影响，例如 由性染色体编码的基因和性腺激素的水平， 成年因为这些类型的性别偏见保护是由不同的 分子机制，区分每个因素的作用位点是第一步 了解性别偏见保护是如何运作的拟议研究 包括全脑磁共振成像来测量每个大脑的大小 在特定性别偏见因素可以严格确定的条件下， 观察它们各自的效果。性染色体非整倍体的脑 和野生型（XO、XX、XY和XXY）将在小鼠具有或不具有 它们的生殖腺实验设计将确定哪些性别差异在体积 大脑区域的数量受到X染色体数量的影响， 缺乏Y染色体，以及睾丸和卵巢分泌物的水平， 成年研究结果将建立大脑区域和局部功能， 受到不同性别偏见机制的影响。结果将改变概念 研究受影响脑区保护机制的框架 神经和精神疾病。