Developmental Stress and Vulnerability to Brain Injury

发育压力和脑损伤的脆弱性

基本信息

批准号：
6806975
负责人：
MICHAEL J ZIGMOND
金额：
$ 11.13万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-09-30 至 2006-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6806975
关键词：
Africa behavioral /social science research tag brain injury developmental neurobiology developmental nutrition early experience laboratory rat mother deprivation neurotoxins nutrition related tag stress training

项目摘要

DESCRIPTION (provided by applicant): Overall hypothesis: Exposure of developing animals to severe stress causes an increase in the vulnerability of the brains of those animals to neuronal death, which persists into adulthood, leading to an increase in the susceptibility to neurological and psychiatric disease. Possible routes of rehabilitation include environmental enrichment, exercise, and specialized diets. We are seeking funds to further develop the tools necessary for collaborative studies on the impact of developmental stress and the vulnerability of the adult brain to neurotoxin exposure. Over the next two years, we have three major Specific Aims: Aim 1: To develop models of developmental stress in laboratory rats. Three models will be explored: (a) maternal deprivation, (b) nutritional deprivation, and (c) an inflammatory challenge. Aim 2: To obtain pilot data to see if developmental stress increases the vulnerability of the brain to neurotoxins. We will determine whether developmental stress increases the damage done by application of such neurotoxins as quisqualic acid and 6-hydroxydopamine. Special attention will be given to dopamine neurons in the brain, although other types of neurons also will be examined. Both behavioral and neurobiological indices of damage will be monitored. Aim 3: To further develop the research capacity of the University of Cape Town and the University of Stellenbosch through (a) attendance by faculty and trainees at international meetings, (b) attendance of key individuals at specific courses on research methodology, and (c) provision of instruction to faculty and trainees other professional skills such as oral and written communication, applying for research funds, and responsible conduct of research. Having accomplished these aims in 2003-2005 (FY 04 and FY05), we will submit a full proposal for research to begin in July 2005 (FY 06) that utilizes these tools to explore the molecular and cellular basis of DA neuron cell death and protection. Moreover, the methods and reagents that we develop will be made available to others in the field.

描述（由申请人提供）：总体假设：发育中的动物暴露在严重压力下会导致这些动物大脑对神经元死亡的脆弱性增加，这种情况持续到成年期，导致对神经和精神疾病的易感性增加。可能的康复途径包括丰富环境、锻炼和特殊饮食。我们正在寻求资金，以进一步开发必要的工具，以开展合作研究，研究发育压力的影响和成人大脑对神经毒素暴露的脆弱性。在接下来的两年里，我们有三个主要的具体目标：目标 1：开发实验室大鼠的发育应激模型。将探讨三种模型：（a）孕产妇剥夺，（b）营养剥夺，以及（c）炎症挑战。目标 2：获得试点数据，看看发育压力是否会增加大脑对神经毒素的脆弱性。我们将确定发育压力是否会增加使用使君子酸和 6-羟基多巴胺等神经毒素造成的损害。尽管其他类型的神经元也将受到检查，但我们将特别关注大脑中的多巴胺神经元。行为和神经生物学损伤指数都将受到监测。目标 3：通过以下方式进一步发展开普敦大学和斯泰伦博斯大学的研究能力：(a) 教师和学员参加国际会议，(b) 关键人物参加研究方法的具体课程，以及 (c) ）向教师和学员提供其他专业技能的指导，例如口头和书面沟通、申请研究基金以及负责任地进行研究。在 2003-2005 年（2004 财年和 2005 财年）实现这些目标后，我们将提交一份完整的研究提案，该提案将于 2005 年 7 月（2005 财年）开始，利用这些工具探索 DA 神经元细胞死亡和保护的分子和细胞基础。此外，我们开发的方法和试剂将提供给该领域的其他人。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Effect of exercise on dopamine neuron survival in prenatally stressed rats.

DOI：
10.1007/s11011-009-9161-6
发表时间：
2009-12
期刊：
METABOLIC BRAIN DISEASE
影响因子：
3.6
作者：
Mabandla, Musa V.;Kellaway, Lauriston A.;Daniels, William M. U.;Russell, Vivienne A.
通讯作者：
Russell, Vivienne A.

Early pubertal female rats are more resistant than males to 6-hydroxydopamine neurotoxicity and behavioural deficits: a possible role for trophic factors.

青春期早期雌性大鼠比雄性大鼠对 6-羟基多巴胺神经毒性和行为缺陷具有更强的抵抗力：营养因子的可能作用。