Adult Neurogenesis & Alcohol-Induced Learning Deficits

成人神经发生

• 批准号: 7140473
• 负责人: Lee Anna Cunningham
• 金额: $ 20.86万
• 依托单位: UNIVERSITY OF NEW MEXICO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-18 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7140473
• 关键词: behavioral /social science research tag; confocal scanning microscopy; developmental disease /disorder; developmental neurobiology; disease /disorder model; early experience; embryo /fetus toxicology; ethanol; fetal alcohol syndrome; hippocampus; immunocytochemistry; laboratory mouse; learning disorders; longitudinal animal study; mature animal; neurogenesis; polymerase chain reaction

DESCRIPTION (provided by applicant): The denate gyrus of the hippocampus is an area where new neurons continue to be generated throughout adult life. Although the role of adult hippocampal neurogenesis is still debated, accumulating evidence suggests that it is involved in the acquisition of certain forms of hippocampal-dependent learning. Based on those findings, we have begun to explore the relationship between learning deficits and neurogenesis in adult offspring of prenatal ethanol exposed rodents. For these studies, we have utilized a mouse model of fetal alcohol exposure (FAE) that is based on free-choice and represents a moderate alcohol access model of FAE. Adult offspring of FAE mice display learning deficits similar to that of the FAE rat, but the FAE mouse model is not confounded by potential diet and pair feeding effects. Preliminary data presented in this proposal demonstrate that FAE does not impair basal neurogenesis under standard housing conditions, but abolishes the neurogenic response to enriched environment. Studies outlined in this exploratory R21 proposal are designed to determine a) whether FAE also impairs the neurogenic response to hippocampal-dependent learning, and b) whether mitigation of the neurogenic response to behavioral challenge is due to intrinsic defects of FAE progenitors and/or due to microenvironmental changes within the neurogenic niche of the adult SGZ. Our preliminary studies are among the first to demonstrate that prenatal exposures can result in persistent defects in adult hippocampal neurogenesis. Since learning disabilities are among the most prevalent and pervasive fetal alcohol-related defects in children, further studies to understand the basis of these deficits in animal models of prenatal ethanol exposure seems warranted.

描述（由申请人提供）：海马体的退化回是在整个成年过程中不断产生新神经元的区域。尽管成人海马神经发生的作用仍然存在争议，但越来越多的证据表明，它参与了某些形式的海马依赖性学习的获得。基于这些发现，我们开始探索产前乙醇暴露的啮齿动物成年后代的学习缺陷和神经发生之间的关系。在这些研究中，我们使用了胎儿酒精暴露 (FAE) 小鼠模型，该模型基于自由选择，代表了 FAE 的中度酒精接触模型。 FAE 小鼠的成年后代表现出与 FAE 大鼠相似的学习缺陷，但 FAE 小鼠模型不会受到潜在饮食和配对喂养效应的影响。该提案中提供的初步数据表明，FAE 不会损害标准住房条件下的基础神经发生，但会消除对丰富环境的神经发生反应。本探索性 R21 提案中概述的研究旨在确定 a) FAE 是否也会损害对海马依赖性学习的神经源性反应，以及 b) 对行为挑战的神经源性反应的缓解是否是由于 FAE 祖细胞的内在缺陷和/或由于成体 SGZ 神经源性生态位内微环境的变化。我们的初步研究是最早证明产前暴露可能导致成人海马神经发生持续缺陷的研究之一。由于学习障碍是儿童中最普遍和普遍的胎儿酒精相关缺陷之一，因此似乎有必要进一步研究以了解产前乙醇暴露动物模型中这些缺陷的基础。