Molecular regulation of estrogen receptor gene expression in the adult brain

本研究探讨了关键基因在男性和女性大脑中的差异调控的分子机制。雌性激素对于男性和女性大脑的结构和功能方面都是至关重要的。雌激素通过介导其作用的细胞内受体发挥作用。雌性激素受体基因在神经损伤后在男性和女性大脑中的表达受到不同的调控，然而，调控这种表达的分子机制尚不清楚。在本研究中，我们将在大鼠动物模型中检测DNA表观遗传修饰对脑损伤后雌激素受体表达的影响。分子生物学和组织学技术将用于识别这些变化。假设损伤后雌激素受体基因表达受DNA去甲基化的差异激活。这项研究的结果将加强对大脑中基因表达调节的内在性别差异的理解。该项目将神经内分泌学领域与快速发展的表观遗传学领域结合起来。除了回答神经科学领域的基本问题外，本研究的影响还因多个本科生、研究生和博士后的参与而增强，该研究为这些学生提供了基础的科学背景。学生们参与了这个项目的各个方面，从进行实验到展示发现。将鼓励所有学生在大学活动以及其他区域和国家会议上介绍他们的数据。学生也有机会参加社区活动，如与神经科学协会的大脑意识周相关的活动。这些活动让学生与公众互动，教育孩子和家长了解他们的大脑如何运作的重要性。

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.