Molecular regulation of estrogen receptor gene expression in the adult brain

成人大脑雌激素受体基因表达的分子调控

• 批准号: 1121129
• 负责人: Melinda Wilson
• 金额: $ 47.4万
• 依托单位: University of Kentucky Research Foundation
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-15 至 2015-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1121129&HistoricalAwards=false
• 关键词: Molecular; regulation; estrogen; receptor; gene

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.

本研究探讨了关键基因在男性和女性大脑中差异调节的分子机制。 激素，雌激素，对于建立男性和女性大脑的结构和功能方面至关重要。 雌激素通过介导其作用的细胞内受体发挥作用。 雌激素受体基因的表达在神经损伤后的男性和女性大脑中受到不同的调节，然而，调节这种表达的分子机制尚不清楚。 在这项研究中，将在大鼠动物模型中检查DNA的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。 据推测，雌激素受体基因表达的差异激活DNA去甲基化损伤后。 这项研究的结果将增强对大脑基因表达调控中固有的性别差异的理解。 该项目结合了神经内分泌学领域和迅速发展的表观遗传学领域。 除了回答神经科学领域的基本问题外，本研究的影响还通过多名本科生，研究生和博士后学生在研究过程中的参与来增强，为这些学生提供基本的科学背景。学生们参与了这个项目的各个方面，从实验到展示结果。将鼓励所有学生在大学活动以及其他区域和国家会议上展示他们的数据。 学生也有机会参加社区活动，如与大脑意识周与神经科学协会。 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。