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调查各种健康干预措施的动物实验。动物研究的一个潜在的令人困惑的问题是，大多数研究动物的典型饲养方式导致极端缺乏身体活动。新兴的静止生理学领域提供了理论和证据，迫使科学家重新评估实验室动物的典型饲养方式。这项拟议的研究将解决这样的假设，即与定期锻炼(EX)或间歇性体力活动(PA)的动物相比，不能在标准笼子外锻炼(SED)的动物的基因表达受到上调(&gt；1.4)或下调(&lt；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、肿瘤发展和痴呆症；这些组之间的基因表达差异不会在3个月后出现，而是在9个月后出现，不同的表型将在9个月或之后出现。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16个月的数据集进行比较，以确定与间歇性体育活动或定期锻炼的动物相比，不参加体力活动的动物是否表现出不同的基因表达水平和/或表型。这些实验将1)告诉我们在生命周期中，关键基因表达水平和特定蛋白质因从事体育活动或锻炼而发生变化的时间；2)比较三个不同年龄组中与这些基因表达相关的表型(例如心血管风险因素、肿瘤发展、学习和记忆)；3)确定在实验室大鼠的典型寿命内，年龄与是否接受笼外不活动、间歇性体育活动或定期运动对健康和疾病的影响。这些结果可能会显著改变长期健康和干预研究中动物实验的设计策略。

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.