Oxymax System with Teadmill for Quantifying Exercise in Mice

描述（由申请人提供）：我们正在申请资金，以获得一个Oxymax快速系统与硬件和跑步机（哥伦布仪器公司），这将允许多个用户进行能量消耗和燃料利用的研究运动小鼠。这些措施可以同时在8只老鼠身上进行，将允许定量评估和比较运动表现对各种参数的反应，包括衰老，基因修饰和药物治疗。该项目负责人尼尔·鲁德曼（Neil Ruderman）博士率先将运动应用于人类2型糖尿病的治疗，并首次在啮齿动物身上证明了运动能显著提高骨骼肌的胰岛素敏感性。最近，他的研究小组已经表明，运动的这些和其他影响很可能在很大程度上是由燃料感应酶amp活化蛋白激酶（AMPK）介导的。Ruderman实验室将使用Oxymax系统和跑步机来检查运动对SIRT1/LKB1/AMPK/eNOS信号机制的急性和慢性影响，他们最近在小鼠主动脉内皮中发现了SIRT1/LKB1/AMPK/eNOS信号机制，目前正在其他组织中研究。该研究将对初步数据进行后续研究，这些数据表明，这种机制是通过运动急性激活的，并将探索在SIRT1、eNOS或LKB1内皮细胞特异性敲低的小鼠中，这种机制和运动能力是如何改变的。在与Ruderman小组的合作中，Cohen博士将确定在喂食高脂高糖饮食的LDLR-/-小鼠中，常规运动减少动脉粥样硬化的能力是否会在基因上缺乏SIRT1或其他信号之一的小鼠中减弱。此外，沃尔什博士将研究这些基因改变对肌肉和脂肪组织中缺血诱导血管生成的影响。Bhasin博士将研究在性腺功能减退的啮齿动物模型中，运动与雄激素补充在协同激活合成代谢信号中的作用。该仪器还将用于检查运动对患有代谢性心脏病和心肌功能障碍的小鼠的有益作用的基础（Colucci），睾酮在小鼠衰老过程中提高运动表现的能力（Bhasin和Jasuja），以及过度表达和敲除肌肉生长抑制素对运动表现的影响（Bhasin和Guo）。在其他研究中，坎德尔博士将研究运动增加啮齿动物小脑葡萄糖摄取的机制。Seldin和Jasuja将对一只酪蛋白激酶2的四个亚基中有三个基因缺失的老鼠进行研究。这些老鼠的特点是身体脂肪减少，食物摄入量增加，体温升高，运动能力下降。除了用于这些研究之外，我们预计oxymax跑步机将更紧密地联系使用它的研究人员的研究，基于他们对运动和运动产生的信号事件的共同兴趣。

DESCRIPTION (provided by applicant): We are requesting funds to obtain an Oxymax Fast System with hardware and treadmills (Columbus Instruments) that would allow multiple users to carry out studies on energy expenditure and fuel utilization in exercising mice. Such measures, which can be performed concurrently on 8 mice, will allow quantitative assessment and comparison of exercise performance in response to a wide variety of parameters including aging, genetic modifications and drug therapy. The PI, Dr. Neil Ruderman, pioneered the use of exercise in the treatment of type 2 diabetes in humans and first demonstrated in rodents that exercise acutely increases insulin sensitivity in skeletal muscle. Most recently, his group has shown that these and other effects of exercise are very likely mediated, in great measure, by the fuel sensing enzyme AMP-activated protein kinase (AMPK). The Ruderman lab will use the Oxymax system with treadmills to examine the acute and chronic effects of exercise on the SIRT1/LKB1/AMPK/eNOS signaling mechanism that it has recently identified in the endothelium of the mouse aorta and is presently studying in other tissues. It will follow up on preliminary data suggesting that this mechanism is activated acutely by exercise and will explore how it and the capacity to exercise are altered in mice with endothelial-cell specific knockdown of SIRT1, eNOS or LKB1. In a collaborative effort with the Ruderman group, Dr. Cohen will determine whether the ability of regular exercise to diminish atherosclerosis in LDLR-/- mice fed a high fat-high sucrose diet is attenuated in mice genetically lacking SIRT1 or one of the other signals. In addition, Dr. Walsh will examine the effect of these genetic alterations on ischemia-induced angiogenesis in muscle and adipose tissue. Dr. Bhasin will examine the role of exercise in conjunction with androgen supplementation in synergistic activation of anabolic signaling in the rodent models of hypogonadism. The instrument will also be used to examine the basis for the beneficial effects of exercise in mice with metabolic heart disease and myocardial dysfunction (Colucci)~ the ability of testosterone to enhance exercise performance in mice as they age (Bhasin and Jasuja)~ and the effects of overexpression and knockout of the myokine myostatin on exercise performance ( Bhasin and Guo). In other investigations, Dr. Kandror will examine the mechanism by which exercise increases glucose uptake in the rodent cerebellum in vivo and Drs. Seldin and Jasuja will carry out studies of a mouse with genetic deletion of three of the four subunits of casein kinase 2. These mice are characterized by diminished body fat, increased food intake and body temperature and a decreased ability to exercise.In addition to its use for these studies, we anticipate the oxymax treadmill apparatus will more closely link the research of the investigators who use it, based on their common interests in both exercise and the signaling events that it produces.