UF PASS: Regulation of exercise transducers

UF PASS：运动传感器的调节

基本信息

批准号：
9246861
负责人：
Karyn A Esser
金额：
$ 2.25万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-12-15 至 2022-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9246861
关键词：
Acute Age Animal Model Animals Apoptosis Autophagocytosis Blood Body Composition Body Weight Brain Cells Chemicals Chronic Disease Collection Custom Darkness Data Data Collection Databases Dependovirus Disease Exercise Female Florida Frequencies Genes Genetic screening method Goals Guidelines Harvest Health Home environment Human Informatics Ischemia Kidney Length Libraries Location Maps Methods Modeling Molecular Monitor Muscle Muscle Cells Neurons Outcome Oxidative Stress Phase Physical activity Physiological Protocols documentation Quality Control Rattus Rattus norvegicus Regulation Reperfusion Therapy Reporter Running Sampling Scientist Sepsis Ships Site Skeletal Muscle Small Interfering RNA Stimulus Stress System Techniques Technology Testing Therapeutic Time Tissue Banks Tissues Training Training Programs Transducers United States National Institutes of Health Universities VO2max Work base cohort endoplasmic reticulum stress endurance exercise experimental study expression vector gain of function high throughput screening improved in vivo kidney cell male novel overexpression oxidant stress phase 1 study phase 2 study physical model pre-clinical preconditioning prevent release factor resistance exercise response screening secondary outcome strength training stress tolerance treadmill

项目摘要

Abstract Exercise is a powerful and pleiotropic physiological stimulus that helps prevent many chronic diseases and is used as a therapeutic for disease. While the beneficial effects of exercise are extensively acknowledged there is still very little understood about the molecular transducers of the systems-wide effects. The goal of this University of Florida Molecular Transducers of Physical Activity Preclinical Animal Study Sites application (UF PASS) is to conduct experiments in animals that will provide tissues/blood (i.e. biospecimens) to the Chemical Analysis Sites for identification of molecular transducers induced by defined models of physical activity from tissues that cannot be obtained from humans as well as to conduct mechanistic studies that can support screening of novel transducers to quickly move the field forward. In Phase 1, UF PASS proposes to collect biospecimens for the Chemical Analysis sites following endurance (run-training) or resistance exercise protocols on male and female Fischer 344xBrown Norway rats (F344-BN) at three different ages. To better capture the dynamics of the exercise/adaptation responses we propose to: 1) Collect biospecimens at 5 selected timepoints following an acute bout of exercise on naïve and trained rats; 2) Collect biospecimens following short duration training (after 5 bouts) and 3) Collect biospecimens following long-term (8 weeks) training. For Phase 2, our hypothesis is that factors released from muscle (i.e. myokines) are the molecular transducers that function throughout the system to improve the well-established stress tolerance. The goal of these studies will be to employ high throughput screening technologies to test up to 1500 myokines. We will then use secondary screening techniques to test 100 candidates from which we will select up to 3 candidates for in vivo testing. The results of the experiments in Aim 3 will provide molecular evidence identifying a set of transducers, released from muscle, that are necessary for exercise induced systemic health. The goals of the UF PASS will be pursued by the following Specific Aims: Specific Aim 1: Center Coordination Phase. Specific Aim 2: Phase 1 Studies. To perform endurance and resistance exercise using male and female F344BN rats at 3-4, 16-18, and 27-29 mo. Specific Aim 3: Phase 2 Studies. The goal in Aim 3 is to test myokines as the exercise transducers for improved stress tolerance.

摘要运动是一种强大的、多效性的生理刺激，有助于预防许多慢性疾病。疾病并被用作疾病的治疗方法，而运动的有益作用是广泛的。承认人们对全系统效应的分子传感器知之甚少。佛罗里达大学体力活动分子传感器临床前动物研究的目标场地申请（UF PASS）是在动物身上进行实验，提供组织/血液（即生物样本）到化学分析站点，用于识别由定义的诱导的分子传感器无法从人体获得的组织的身体活动模型以及进行机制研究可以支持新型传感器的筛选，从而快速推动该领域向前发展。在第一阶段，UF PASS 建议在耐久后为化学分析站点收集生物样本对雄性和雌性 Fischer 344xBrown 挪威大鼠 (F344-BN) 进行（跑步训练）或阻力运动方案为了更好地捕捉运动/适应反应的动态，我们建议： 1) 在对幼鼠和经过训练的大鼠进行急性运动后，在 5 个选定的时间点收集生物样本； 2) 在短期训练后（5 轮后）收集生物样本，以及 3) 在以下训练后收集生物样本长期（8周）培训。对于第二阶段，我们的假设是肌肉释放的因子（即肌因子）是分子传感器这些研究的目标是在整个系统中发挥作用，以提高既定的压力耐受力。我们将采用高通量筛选技术来测试多达 1500 个肌因子。二次筛选技术，用于测试 100 名候选者，我们将从中选择最多 3 名候选者进行体内试验目标 3 中的实验结果将提供识别一组传感器的分子证据，从肌肉中释放，这是运动引起的全身健康所必需的。通过以下具体目标来实现：具体目标 1：中心协调阶段。具体目标 2：第一阶段研究使用男性和女性进行耐力和阻力训练。 3-4、16-18 和 27-29 个月的 F344BN 大鼠。具体目标 3：第 2 阶段研究目标 3 的目标是测试肌因子作为运动传感器。提高抗压能力。