Estrogen Receptor Beta in the Developing Prefrontal Cortex

发育中的前额皮质中的雌激素受体β

• 批准号: 1551724
• 负责人: Robert Handa
• 金额: $ 48.59万
• 依托单位: Colorado State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-01 至 2019-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1551724&HistoricalAwards=false
• 关键词: Estrogen; Receptor; Beta; Developing; Prefrontal

The steroid estrogen regulates many functions of the brain including behavior and cognition, while the prefrontal cortex (PFC) is a brain region that controls aspects of cognitive function and emotional behavior. Not surprisingly the PFC is estrogen sensitive, but there is currently little known about how it responds to estrogen. The goal of this research is therefore to determine how estrogen regulates the PFC. The research tests the prediction that of the two main types of estrogen receptors, alpha and beta, that the PFC is regulated by beta (ERb). Successful completion of these studies will provide novel information about an important but unexplored neuronal phenotype in the PFC. Innovative approaches are used to examine ERb neurons and the results of these studies can impact multiple research arenas. This research project will be used for the training of high school, undergraduate and graduate students, particularly underrepresented minorities, in neuroscience. Results will be disseminated through peer-reviewed publication and by student presentations at local and national meetings. These studies explore the function of a select group of cells in the mouse PFC that express ERb. The PFC controls many behaviors including cognition, attention, and neuroendocrine stress responses. Estrogen can alter the development of this brain region, yet, little is known of the neurons in the PFC that express ERb, partly due to the absence validated reagents allowing the detection of ERb in brain. The proposed studies will examine this group of neurons in the PFC using a novel transgenic mouse that express a fluorescent protein in ERb neurons. Preliminary results show that the location of ERb expressing neurons changes across development of the PFC. Studies in this application will address the hypothesis that these changes reflect developmental alterations in estrogen sensitivity in different cortical layers across time. Using anatomical approaches, these studies will determine the identity of the cortical neurons that express ERb. Next, molecular approaches will be used to address the reason why estrogen receptor levels change in amount and location during cortical development and lastly, the function of identified ERb neurons in the PFC will be examined using electrophysiology

类固醇雌激素调节大脑的许多功能，包括行为和认知，而前额叶皮层（PFC）是控制认知功能和情感行为的大脑区域。PFC对雌激素敏感并不奇怪，但目前对它如何对雌激素做出反应知之甚少。因此，本研究的目的是确定雌激素如何调节PFC。 该研究测试了两种主要类型的雌激素受体α和β的预测，即PFC受β（ERb）调节。 这些研究的成功完成将提供新的信息，一个重要的，但未开发的神经元表型在PFC。创新的方法被用来检查ERb神经元，这些研究的结果可以影响多个研究领域。该研究项目将用于培训高中，本科和研究生，特别是代表性不足的少数民族，在神经科学。 研究结果将通过同行评审的出版物以及学生在地方和国家会议上的发言进行传播。这些研究探索了小鼠PFC中表达ERb的一组选定细胞的功能。 PFC控制许多行为，包括认知，注意力和神经内分泌应激反应。雌激素可以改变该脑区的发育，然而，PFC中表达ERb的神经元知之甚少，部分原因是缺乏允许检测脑中ERb的经验证的试剂。 拟议的研究将使用在ERb神经元中表达荧光蛋白的新型转基因小鼠来检查PFC中的这组神经元。 初步结果表明，ERb表达的神经元的位置的变化，在整个发展的PFC。在本申请中的研究将解决的假设，这些变化反映了雌激素敏感性在不同的皮质层随时间的发展变化。使用解剖学方法，这些研究将确定表达ERb的皮质神经元的身份。接下来，将使用分子方法来解决皮质发育过程中雌激素受体水平在数量和位置上变化的原因，最后，将使用电生理学检查PFC中鉴定的ERb神经元的功能