This study investigates the molecular mechanisms by which critical genes are differentially regulated in the male and female brain. The hormone, estrogen, is critical for establishing structural and functional aspects of the brain in both males and females. Estrogen functions through intracellular receptors that mediate its action. Estrogen receptor gene expression is regulated differently in the male and female brain after a neural injury, however, the molecular mechanisms that regulate this expression are not known. In this study, the effects of epigenetic modification of DNA on the expression of estrogen receptors after brain injury will be examined in a rat animal model. Molecular biological and histological techniques will be used to identify these changes. It is hypothesized that estrogen receptor gene expression is differentially activated by DNA demethylation after injury. The results of this study will enhance the understanding of the inherent gender differences in the regulation of gene expression in the brain. This project combines the fields of neuroendocrinology with the rapidly growing field of epigenetics. In addition to the answering fundamental questions in the field of neuroscience, the impact of this study is enhanced by the involvement of multiple undergraduate, graduate, and postdoctoral students over the course of the study that provides a fundamental scientific background to these students. The students are involved in all aspects of this project from performing experiments to presenting the findings. All students will be encouraged to present their data at University events as well as at other regional and national meetings. Students also have the opportunity participate in community events such as those associated with Brain Awareness Week with the Society for Neuroscience. These events allow students to interact with the public to educate children and parents alike to importance of understanding how their brains function.