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取决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混淆问题是，大多数研究动物的典型圈养方式导致极端的身体活动。新兴的不活动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。这项拟议中的研究将解决这样一个假设，即在标准笼子（SED）外无法进行运动的动物的基因表达将增加。（>1.4）或下降（<0.7）与有规律的运动（EX）或间歇性体力活动（PA）的动物相比受到调节;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;并且各组之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，并且不同的表型将在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、海马和乳腺组织中的基因表达和特异性蛋白质，并将基因型和表型数据与我们的16个月数据集进行比较，以确定与进行间歇性体力活动或定期锻炼的动物相比，没有进行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何时因身体活动或锻炼而发生变化; 2）比较与这些基因表达相关的表型（如心血管危险因素、肿瘤发展、学习和记忆）;和3）确定年龄和在笼外无活动、间歇性体力活动或规律锻炼对实验室大鼠典型寿命期间的健康和疾病的影响。这些结果可能会显着改变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.