Functional implications of stress-evoked changes in epigenetic mechanisms

应激引起的表观遗传机制变化的功能意义

• 批准号: 1146853
• 负责人: Laura Schrader
• 金额: $ 37.5万
• 依托单位: Tulane University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-01 至 2015-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1146853&HistoricalAwards=false
• 关键词: Functional; implications; stress; evoked; changes

Prolonged or repeated stress leads to allostatic overload that mediates various cellular changes in the hippocampus, the area of the brain important for learning and memory. These changes result in reduced hippocampus function and deficits in learning and memory. Chronic stress-mediated memory deficits in humans and animals are well documented. Less is known about the molecular mechanisms underlying adverse effects that cause reduced hippocampus function in response to chronic stress. It is becoming increasingly evident that dynamic changes to the histones, the proteins that DNA is coiled around, are molecular mechanisms important for the physiological reaction to environmental stressors. Deciphering information encoded in histone modifications in the hippocampus in response to chronic stress is critical for understanding the molecular mechanisms of regulation of memory by stress. This project will identify novel histone changes that are modulated in response to chronic stress and negatively impact hippocampus function. Furthermore, the project is designed to investigate the effects on memory as the functional output of these modifications. By studying epigenetic changes and the mechanisms of these changes, these studies will define a novel common point of convergence as a mechanism to control transcription of genes that are regulated by stress and involved in learning and memory. Such information will fill the gap connecting histone modifications in the hippocampus to memory impairments caused by chronic stress. Students working in this lab will gain valuable research experience at the undergraduate, masters, and doctoral levels. These students participate in experiment planning, performance and analysis, as well as manuscript preparation and presentation at national and international meetings. Training provided by the research in this proposal is particularly important for science education in Louisiana, which is currently designated as an NSF EPSCOR state.

长时间或反复的压力会导致适应过载，从而介导海马体中各种细胞变化，海马体是大脑中对学习和记忆很重要的区域。这些变化导致海马体功能下降，学习和记忆能力下降。慢性应激介导的记忆缺陷在人类和动物中有很好的记录。在慢性应激反应中，导致海马功能降低的不良反应的分子机制尚不清楚。越来越明显的是，组蛋白（DNA盘绕的蛋白质）的动态变化是对环境应激源的生理反应很重要的分子机制。破译海马对慢性应激反应中组蛋白修饰编码的信息对于理解应激调节记忆的分子机制至关重要。该项目将确定新的组蛋白变化，这些变化在慢性应激反应中被调节，并对海马功能产生负面影响。此外，该项目旨在研究这些修改的功能输出对记忆的影响。通过研究表观遗传变化和这些变化的机制，这些研究将定义一个新的共同趋同点，作为控制受压力调节的基因转录的机制，并参与学习和记忆。这些信息将填补海马体中组蛋白修饰与慢性压力引起的记忆障碍之间的空白。在本实验室工作的学生将获得在本科、硕士和博士阶段的宝贵研究经验。这些学生参与实验计划，性能和分析，以及手稿的准备和在国内和国际会议上的演讲。本提案中的研究提供的培训对路易斯安那州的科学教育尤其重要，路易斯安那州目前被指定为NSF EPSCOR州。