Discriminating sex chromosome and hormonal effects on brain sexual dimorphisms

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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.