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Molecular regulation of estrogen receptor gene expression in the adult brain

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
依托单位国家:
美国
项目类别:
Continuing Grant
财政年份:
2011
资助国家:
美国
项目状态:
已结题
起止时间:
2011-08-15 至 2015-07-31

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中文摘要
翻译
这项研究调查了关键基因在男性和女性大脑中差异调控的分子机制。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。雌激素通过调节其作用的细胞内受体发挥作用。在神经损伤后,雌激素受体基因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。在这项研究中,将在一个大鼠动物模型中检测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被用来识别这些变化。推测损伤后DNA去甲基化对雌激素受体基因表达具有差异性激活作用。这项研究的结果将加强对大脑中基因表达调控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增长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,在为这些学生提供基本科学背景的研究过程中,多名本科生、研究生和博士后的参与增强了本研究的影响。学生们参与了这个项目的方方面面,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。学生们还有机会参加社区活动,如与神经科学学会的大脑意识周相关的活动。这些活动允许学生与公众互动,教育孩子和家长了解他们大脑如何运作的重要性。
英文摘要
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.
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Developmental regulation of estrogen receptor-alpha by epigenetic modification
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