Development Stress, Exercise, and Vulnerability to Neuronal Injury

描述（申请人提供）：代表匹兹堡大学和南非两个机构的研究人员，开普敦大学和斯泰伦博斯大学正在寻求资金，作为我们机构之间整体努力的一部分，以研究有关环境对大脑和行为的影响的特定假设，并帮助在开普敦的学术界建立一个区域卓越中心，神经科学和专业技能培训。他们的假设是，发育中的动物暴露于严重的压力将对大脑产生显著的有害影响，并增加其对神经元死亡的脆弱性，但这可以通过运动干预计划来抵消。有五个具体目标：四个是研究目标，一个是一套能力建设目标。研究目的：目的1 -通过使用蛋白质组学筛选，研究发育应激源（母亲分离）对与大脑脆弱性相关的几个变量的影响，包括（a）下丘脑-垂体-肾上腺（HPA）轴，（B）线粒体功能，和（c）一类特定蛋白质（神经营养因子）的改变。目标2 -此外，将仔细检查中枢多巴胺神经元的状态。目的3 -检查运动（自愿运行）对这些相同的变量的影响，然后确定是否可以通过以后暴露于运动抵消产妇分离的影响。目的4 -使用6-羟基多巴胺作为应激源，检查母体分离对多巴胺能神经元对氧化应激的脆弱性的影响，然后确定母体分离引起的脆弱性增加是否可以通过运动来抵消。目标5 -能力建设目标：进一步发展开普敦大学和斯泰伦博斯大学以及西开普省其他机构的研究能力，办法是教员和受训人员参加国际会议，参加关于研究方法的具体课程，并提供其他专业技能方面的指导，如口头和书面交流，申请研究基金，和负责任的研究行为。研究小组认为，他们的研究项目将为更广泛地了解表观遗传对行为和大脑功能的影响提供重要见解，并为促进南部非洲两个关键机构的研究能力提供背景。

DESCRIPTION (provided by applicant): Researchers representing the University of Pittsburgh and two institutions in South Africa, the University of Cape Town and the University of Stellenbosch are seeking funds as part of an overall effort between our institutions to examine a specific hypothesis pertaining to the impact of environment on brain and behavior and also to help create within the academic community in Cape Town a regional center of excellence in neuroscience and in professional skill training. Their hypothesis is that exposure of developing animals to severe stress will have a significant detrimental effect on brain and increase its vulnerability to neuronal death, but that this can be offset through an exercise intervention program. There are five specific aims: four are research aims and one is a set of capacity building objectives. Research objectives: Aim 1 - To examine the impact of a developmental stressor (maternal separation) on several variables related to the vulnerability of the brain, including (a) the hypothalamic-pituitary-adrenal (HPA) axis, (b) mitochondrial function, and (c) alterations in a specific class of proteins (neurotrophic factors) by using a proteomic screen. Aim 2 - In addition, the state of central dopamine neurons will be carefully examined. Aim 3 - To examine the effects of exercise (voluntary running) on these same variables, and then to determine whether the effect of maternal separation can be offset by later exposure to exercise. Aim 4 -To examine the effects of maternal separation on the vulnerability of dopaminergic neurons to oxidative stress using 6- hydroxydopamine as the stressor, then determine whether any increase in vulnerability caused by the maternal separation can be offset by exercise. Aim 5 - Capacity building objectives: To further develop the research capacity of the Universities of Cape Town and Stellenbosch as well as other institutions in the Western Cape through attendance by faculty and trainees at international meetings, participation in specific courses on research methodology, and provision of instruction in other professional skills, such as oral and written communication, applying for research funds, and responsible conduct of research. The research team believes that their research project will provide important insights into epigenetic influences on behavior and brain function more generally, and also serve as a context for promoting the research capacity of two key institutions in southern Africa.