Gene expression and phenotypic consequences of laboratory housing in aging rat

描述（由申请人提供）：生物医学研究的进展依赖于研究各种健康干预措施的动物实验。动物研究的一个潜在的混淆问题是，大多数研究动物的典型饲养方式导致它们极度缺乏身体活动。不活动生理学这一新兴领域提供了理论和证据，迫使科学家们重新评估实验室动物的典型饲养方式。拟议的研究将解决这样一个假设：与定期进行运动（EX）或间歇性体育活动（PA）的动物相比，无法在标准笼子外进行运动的动物（SED）的基因表达会上调（>1.4）或下调（<0.7）；这些基因表达与表型相关，包括与年龄相关的疾病，如心血管疾病、肿瘤发展和痴呆；组间的基因表达差异不会在3个月时出现，而是在9个月时出现，不同的表现型会在9个月时或之后出现。我们计划1)在3个月和9个月时测量心脏组织、海马体和乳腺组织中的基因表达和特定蛋白质，并将基因型和表型数据与我们的16个月数据集进行比较，以确定不进行体育锻炼的动物与进行间歇性体育锻炼或定期锻炼的动物相比，是否表现出不同的基因表达水平和/或表型。这些实验将1)告诉我们，在人的一生中，关键基因表达水平和特定蛋白质在什么时候会因体育活动或锻炼而发生变化；2)比较三个实验组在不同年龄段与这些基因表达相关的表型（如心血管危险因素、肿瘤发生、学习和记忆）；3)确定年龄和笼子外不活动、间歇性体育活动或定期运动对实验室大鼠典型生命周期内健康和疾病的相互作用。这些结果可能会显著改变在长期健康和干预研究中设计动物实验的策略。

DESCRIPTION (provided by applicant): Advances in biomedical research depend on animal experiments that investigate a variety of health interventions. A potential confounding problem with animal studies is that the typical way in which most research animals are housed results in extreme physical inactivity. The emerging field of inactivity physiology has provided theory and evidence that is compelling scientists to reassess the way in which laboratory animals are typically housed. The proposed study will address the hypothesis that animals with no access to exercise outside a standard cage (SED) will have gene expressions that are up (>1.4) or down (<0.7) regulated compared with animals that have regular access to exercise (EX) or intermittent physical activity (PA); that these gene expressions are associated with phenotypes including age-related diseases such as cardiovascular disease, tumor development, and dementia; and that gene expression differences among the groups will not occur at 3 months, instead will occur at 9 months, and that different phenotypes will occur at or after 9 months. We plan to 1) measure gene expression and specific proteins in cardiac tissue, hippocampus, and mammary tissue at 3 and 9 months and compare genotype and phenotype data with our 16 month data set to determine if animals with no access to physical activity demonstrate different gene expression levels and/or phenotypes compared with animals having access to intermittent physical activity or regular exercise. These experiments will 1) tell us when during the life span, key gene expression levels and specific proteins change due to access to physical activity or exercise; 2) compare phenotypes associated with these gene expressions (e.g. cardiovascular risk factors, tumor development, learning and memory) among the three experimental groups at different ages; and 3) determine the interaction of age and access to either no activity outside a cage, intermittent physical activity or regular exercise on health and disease over the typical life span of a laboratory rat. These results could significantly change strategies for designing animal experiments in long-term health and intervention research studies.