Neonatal Rearing and Adult Stress Reactivity in C57BL/6 Mice

C57BL/6 小鼠的新生儿饲养和成年应激反应

• 批准号: 7141516
• 负责人: DAVID B PARFITT
• 金额: $ 7.8万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7141516
• 关键词: adrenocorticotropic hormone; behavior test; behavioral /social science research tag; child rearing; corticosterone; developmental neurobiology; disease /disorder model; early experience; gene expression; genetically modified animals; hormone regulation /control mechanism; laboratory mouse; mature animal; model design /development; mother child interaction; mother deprivation; neural information processing; newborn animals; psychological stressor; stimulus /response; stress; time resolved data

DESCRIPTION (provided by applicant): Experiments in this grant application are designed to build upon classic studies documenting powerful effects of early handling and maternal separation on adult stress-induced hormone secretion. There is a particularly large literature documenting how adverse neonatal experiences have major, long-term effects on the physiology and behavior of many species, including depression in humans. However, little is known about the impact of neonatal rearing environment on future, adult responses to stressful situations in the mouse. Understanding these environmental effects on mouse brain development would allow us to take advantage of powerful genetic tools available in the mouse to determine the interaction between genetic and epigenetic factors governing brain development. Because maternal separation procedures vary, research in this proposal will optimize the parameters of an early life stress model that exerts permanent long-term effects on the hypothalamic-pituitary-adrenal (HPA) axis in adult male C57BL/6 mice. These experiments will characterize the time of day that neonatal early handling has the maximal response on adult behavior,hormone secretion, and mRNA expression, and whether the presence of littermates can buffer the effect of neonatal maternal separation on adult behavior, hormone secretion and mRNA expression in C57BL/6 mice. It is important to note that the early life stress model that alters stress hormone secretion in adult rats may not be the ideal model system for eliciting changes in adult mice. Therefore, the experiments outlined in this proposal are essential before conducting work exploring the influence of environment on genetic mutants on the C57BL/6 strain of mice. At the conclusion of the experiments in this R03 grant, we will understand the importance of critical variables during differential rearing, such as time of day and isolation from siblings, for altering maternal behavior, adult behavior, stress-induced adrenocorticotropin hormone and corticosterone secretion, and mRNA expression of regulators of the HPA axis in the C57BL/6 mouse. Finally, the basic research outlined in this proposal has clinical biomedical relevance and fulfills an aim of NIMH to decrease the burden of mental illness. Increasing evidence suggests that early adverse experience contributes to the etiology of depression, and this mouse differential rearing model could therefore be helpful in understanding how early life stressors alters neural circuitry that then influence an individual's susceptibility to depression.

描述（由申请人提供）：本赠款申请中的实验旨在基于经典研究，记录了早期处理和产妇分离对成人压力引起的激素分泌的强大影响。有一个特别大的文献记录了不良新生儿经历如何对许多物种的生理和行为（包括人类抑郁症）产生重大的长期影响。然而，关于新生儿饲养环境对未来的影响，成年人对小鼠压力状况的反应知之甚少。了解这些对小鼠脑发育的影响将使我们能够利用小鼠中可用的强大遗传工具来确定遗传性和表观遗传因素控制大脑发育的相互作用。由于产妇分离程序有所不同，因此在该提案中进行的研究将优化早期生命应力模型的参数，该模型对成年男性C57BL/6小鼠的下丘脑 - 垂体 - 肾上腺（HPA）轴施加永久性长期影响。这些实验将表征一天中新生儿早期处理对成人行为，激素分泌和mRNA表达的最大反应，以及同窝料同伙的存在是否可以缓解新生儿母体分离对C57BL/6小鼠中成人行为，激素分泌和mRNA表达的影响。 重要的是要注意，改变成年大鼠压力激素分泌的早期生活压力模型可能不是引起成年小鼠变化的理想模型系统。因此，在进行研究探索环境对基因突变体对C57BL/6小鼠菌株的影响之前，本提案中概述的实验至关重要。在此R03赠款中的实验结束时，我们将了解差异饲养过程中关键变量的重要性，例如一天中的时间和兄弟姐妹隔离，改变了孕产妇行为，成人行为，压力诱导的肾上腺皮质激素激素激素和皮质固醇的肾上腺皮质激素和皮质酮的肾上腺皮质酮和皮质酮的分泌，以及HPA轴心的MRNA表达，6. 6. 6. 6-6-6-6-6bumpl/6bly/6-6-6-6-6-6-6-6-6-6-6-6bly/c57bly/c57bmbl in in the the c57bly/c57bly/c57bmbl/c57bly/c57bly/c57bmbl/c57bbl。最后，该提案中概述的基础研究具有临床生物医学相关性，并实现了NIMH的目的，以减轻精神疾病的负担。越来越多的证据表明，早期不良经历有助于抑郁症的病因，因此，这种小鼠差异饲养模型可以帮助理解早期生活压力如何改变神经回路，从而影响个人对抑郁症的敏感性。