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.
Men and women show significant differences in incidence and progression of neural and psychiatric diseases, indicating that factors present in one sex can protect that sex from disease. The proposed research aims to understand which sex-biasing factors influence the size of brain regions throughout the whole brain, increasing understanding of the brain functions that are influenced by different factors. Ultimately understanding the sites and mechanisms of sex-specific protection will lead to better therapy in both sexes.
| Arnold, Arthur P; Disteche, Christine M (2018) Sexual Inequality in the Cancer Cell. Cancer Res 78:5504-5505 |
| Dinarello, Charles Anthony (2018) An Interleukin-1 Signature in Breast Cancer Treated with Interleukin-1 Receptor Blockade: Implications for Treating Cytokine Release Syndrome of Checkpoint Inhibitors. Cancer Res 78:5200-5202 |
