Name: assessment of murine exercise endurance without the use of a shock grid: an alternative to forced exercise
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通过价值评议＃从退伍军人事务部（LSQ）BX001026，并利用资源和设施在弗吉尼亚州普吉特海湾卫生保健系统中，转基因核心资源在卓越华盛顿弥敦道冲击中心的大学老龄化的基本生物学支持（NIA＃5P30AG-013280），和华盛顿糖尿病内分泌科研究中心的大学（美国国立卫生研究院＃P30 DK-17047）。我们感谢辛西娅Pekow DVM和卡里属Koszdin DVM，弗吉尼亚州普吉特海湾，提供对稿件有益的意见。

这里介绍的方法是经弗吉尼亚州普吉特海湾实验动物管理和使用委员会，并符合ILAR指南实验动物护理和使用。 1，实验准备<ol><li>事先决定，如果血液或组织采集后不久锻炼是必要的，并且如果是，确定对这些程序传导运动后​​的时间间隔。例子包括确定运动诱发的激素或细胞因子释放到血液循环中（因此需要采血），确定运动诱发基因物种的（因此需要安乐死其次是组织集合）的表达。如果立即运动后血液或组织集合表示，有材料上的手在操作室这些程序。接收机构审查委员会的批准，并根据监管指引执行。并非所有的实验需要运动后血液或组织本站统计上;耐力跑一个简单的比较可能是所有需要。 </li><li>决定提前对实验组和运动后的程序老鼠（见上面的说明）。 </li><li>放置在一个坚固的桌子跑步机在一个安静的房间里跑试验，在此过程中专用的。 </li><li>置的跑步机鼠标大小的车道，并在适当的协议的倾斜。 +5Ø倾斜在这里用来避免在下坡行驶中发生肌肉损害，由于离心运动（拉长肌肉的同时收缩的）。 </li><li>将下面的跑步机带的吸水垫抓屎。 </li></ol> 2，锻炼小鼠跑步机确定是否是"久坐"（不锻炼组）小鼠是必要的，并揭露久坐老鼠的跑步机不运行在2.1步骤概述 - 2.5。决定是否需要2个或4个实验组，， 例如 ，久坐/练习（2组）;行使控制/行使处理（2组，无久坐动物）;或者，久坐不动/行使x控制/处理（4组）。 "治疗"可能是一个转基因或基因敲除，药理疗法，特殊的饮食习惯，或其他实验的干预。 <ol><li>让鼠标适应的操作室中的运输笼，带保持架的队友，1 - 2小时。 </li><li>选择一个单一的鼠标和记录标签号码;鼠标的重量并记录体重。 </li><li>地方小鼠在没有马达跑步机接通驯化，约5分钟。接通电源，无需跑步机带运转，并让小鼠适应的机器噪声另外5分钟。 </li><li>在"久坐"组中删除的小鼠（如果使用的话，见注1）从跑步机上，在这一点上他们回到自己的笼子里，或进行运动后的程序，按照实验设计（见注2）。 </li></ol><ol><li>驯化后，转动传送带以低速（10米/分）时，动物正在探索在皮带和未在该平台上。 </li><li>轻轻拍打或拿起鼠标后躯用压舌板，一至三次，以鼓励不愿意动物留在跑步机上并运行。 注:大多数老鼠都会跑很容易，但他们有时停止的时间很短。发生这种情况时，可使用压舌板轻轻点击或解除动物的后面，以鼓励恢复运行。通常，这些小鼠不需要用压舌板被触摸;注意到手用压舌板对他们的到来使老鼠跑一些。 </li><li>启动一个实验室计时器一次鼠标以10米/分的初始速度运转。 </li><li>转动速度缓慢，当鼠标在顶部（上坡端）的皮带，以1米/分钟，约每2分钟为增量。 </li><li>把速度降下来的如果鼠标反复运行在短脉冲，而不是在稳步前的设置。 </li><li>确定最大持续运行的每个小鼠的速度（一般为14 - 27米/分的C57BL / 6小鼠）通过调节速度和看鼠标。记录这个速度。 注:在跑步机上的动物的位置的线索研究者以动物的意愿以更高的速度运行。如果鼠标在远（上坡）端和即将碰上壁，它已准备好以更高的速度运行。如果鼠标在一个稳定的速度在跑步机上的中间运行它可能是在其最大的速度，或者可能需要进一步调整，根据运行的质量。 </li></ol> 4，端点和鼠标停止<ol><li>用压舌板轻轻敲击或解除该停止动物的后躯，以鼓励恢复运行（见注3.2）。不要停止计时器暂时中断运行。 </li><li>确定并祛瘀ê小鼠拒绝运行。请注意，这在数据表。根据你的实验设计，拒不老鼠可以在不同的日子进行复检 注意:有些老鼠会完全拒绝运行。此类小鼠会在短脉冲时运行，则停止对培育或"踏板"，即，坐在平台上，并使用他们的前腿在皮带上。这些小鼠的姿势弯腰驼背，用自己的四条腿的动物下种植，以防止被击退到跑步机的压舌板。偶尔鼠标变成积极的朝压舌板不愿意何时运行，咬压舌板或爬上它作为逃生的方法。这是第一个5分钟的审判是否鼠标会，或不会，运行中的清晰。卸下拒绝从分析运行，但别指望他们为"久坐"老鼠老鼠。 </li><li>识别耗尽的小鼠和停止计时器。 注:疲劳是由三个连续的降落，并拒绝重新定义庙上运行，尽管温柔的鼓励，再加上疲惫的身体体征，如呼吸困难和张开的姿势。老鼠从疲惫中恢复在30至60分钟。 </li><li>记录的总时间花费在所有的速度运行。 </li><li>根据实验设计，要么返回鼠标是其笼，或进行即时运动后的程序，例如血液或组织采集按机构准则。 </li><li>测试每个人的鼠标，这样前面的老鼠的气味不会影响后续的测试小鼠的行为后擦拭干净带具有杀菌湿巾。 </li><li>测试下一个鼠标。使用新鲜的压舌板每个鼠标。驻留在同一笼小鼠可以在不额外驯化过程间顺序在同一天进行测试。 </li></ol>

<ol>
	<li>Hill, J. A., Wyatt, H. R., Reed, G. W., Peters, J. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Obesity+and+the+environment:+where+do+we+go+from+here?.">Obesity and the environment: where do we go from here?.</a> Science. 299 (5608), 853-855 (2003).</li><li>Kahn, S. E., Hull, R. L., Utzschneider, K. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mechanisms+linking+obesity+to+insulin+resistance+and+type+2+diabetes.">Mechanisms linking obesity to insulin resistance and type 2 diabetes.</a> Nature. 444 (7121), 840-846 (2006).</li><li>Van Gaal, L. F., Mertens, I. L., De Block, C. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mechanisms+linking+obesity+with+cardiovascular+disease.">Mechanisms linking obesity with cardiovascular disease.</a> Nature. 444 (7121), 875-880 (2006).</li><li>Pischon, T., Nothlings, U., Boeing, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Obesity+and+cancer.">Obesity and cancer.</a> Proc Natl Acad Sci USA. 67 (2), 128-145 (2008).</li><li>Benton, C. R., Wright, D. C., Bonen, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=PGC-1&#945;-mediated+regulation+of+gene+expression+and+metabolism:+Implications+for+nutrition+and+exercise+prescriptions.">PGC-1&#945;-mediated regulation of gene expression and metabolism: Implications for nutrition and exercise prescriptions.</a> Appl. Physiol. Nutr. Metab. 33 (5), 843-862 (2008).</li><li>Handschin, C., Spiegelman, B. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+role+of+exercise+and+PGC1alpha+in+inflammation+and+chronic+disease.">The role of exercise and PGC1alpha in inflammation and chronic disease.</a> Nature. 454 (7203), 463-469 (2008).</li><li>Vasunilashorn, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Use+of+the+Short+Physical+Performance+Battery+score+to+predict+loss+of+ability+to+walk+400+meters:+analysis+from+the+InCHIANTI+study.">Use of the Short Physical Performance Battery score to predict loss of ability to walk 400 meters: analysis from the InCHIANTI study.</a> J. Gerontol. A Biol. Med. Sci. 64 (2), 223-229 (2009).</li><li>Wang, Y. X., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Regulation+of+muscle+fiber+type+and+running+endurance+by+PPAR&#948;.">Regulation of muscle fiber type and running endurance by PPAR&#948;.</a> PLoS Bio. 2 (10), e294 (2004).</li><li>LeBrasseur, N. K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Myostatin+inhibition+enhances+the+effects+of+exercise+on+performance+and+metabolic+outcomes+in+aged+mice.">Myostatin inhibition enhances the effects of exercise on performance and metabolic outcomes in aged mice.</a> J. Gerontol. A Biol. Med. Sci. 64 (9), 940-948 (2009).</li><li>Burch, N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Electric+pulse+stimulation+of+cultured+murine+muscle+cells+reproduces+gene+expression+changes+of+trained+mouse+muscle.">Electric pulse stimulation of cultured murine muscle cells reproduces gene expression changes of trained mouse muscle.</a> PLoS ONE. 5 (6), e10970 (2010).</li><li>Li, L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mitochondrial+biogenesis+and+peroxisome+proliferator-activated+receptor-&#947;+coactivator-1&#945;+(PGC-1&#945;)+deacetylation+by+physical+activity.">Mitochondrial biogenesis and peroxisome proliferator-activated receptor-&#947; coactivator-1&#945; (PGC-1&#945;) deacetylation by physical activity.</a> Diabetes. 60 (1), 157-167 (2011).</li><li>Knab, A. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Repeatability+of+exercise+behaviors+in+mice.">Repeatability of exercise behaviors in mice.</a> Physiol. &amp; Behavior. 98 (4), 433-440 (2009).</li><li>He, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=IL-15+Receptor+deletion+results+in+circadian+changes+of+locomotor+and+metabolic+behavior.">IL-15 Receptor deletion results in circadian changes of locomotor and metabolic behavior.</a> J. Mol. Neurosci. 41 (2), 315-321 (2010).</li><li>Wu, X., Hsuchou, H., Kastin, A. J., Rood, J. C., Pan, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Essential+role+of+interleukin-15+receptor+in+normal+anxiety+behavior.">Essential role of interleukin-15 receptor in normal anxiety behavior.</a> Brain Behav. Immun. 24 (8), 1340-1346 (2010).</li><li>Pistilli, E. E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Loss+of+IL-15+receptor+&#945;+alters+the+endurance,+fatigability,+and+metabolic+characteristics+of+mouse+fast+skeletal+muscles.">Loss of IL-15 receptor &#945; alters the endurance, fatigability, and metabolic characteristics of mouse fast skeletal muscles.</a> J. Clin. Invest. 121 (8), 3120-3132 (2011).</li><li>Quinn, L. S., Anderson, B. G., Conner, J. D., Wolden-Hanson, T. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=IL-15+overexpression+promotes+endurance,+oxidative+energy+metabolism,+and+muscle+PPAR&#948;,+SIRT1,+PGC-1&#945;,+and+PGC-1&#946;+expression+in+male+mice.">IL-15 overexpression promotes endurance, oxidative energy metabolism, and muscle PPAR&#948;, SIRT1, PGC-1&#945;, and PGC-1&#946; expression in male mice.</a> Endocrinology. 154 (1), 232-245 (2013).</li><li>Quinn, L. S., Anderson, B. G., Conner, J. D., Wolden-Hanson, T., Marcell, T. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=IL-15+is+required+for+post-exercise+induction+of+the+pro-oxidative+mediators+PPARdelta+and+SIRT1.">IL-15 is required for post-exercise induction of the pro-oxidative mediators PPARdelta and SIRT1.</a> Endocrinology. , (2013).</li><li>Ward, J. M., Anver, M. R., Mahler, J. F., Devor-Henneman, D. E., Ward, J. M., Mahler, J. F., Maronpot, R. R., Sundberg, J. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chapter+13,+Pathology+of+mice+commonly+used+in+genetic+engineering+(C57BL/6;+129;+B6,129;+and+FVB/N).">Chapter 13, Pathology of mice commonly used in genetic engineering (C57BL/6; 129; B6,129; and FVB/N).</a> The Pathology of Genetically Engineered Mice. , 161-179 (2000).</li><li>Lightfoot, J. T., Turner, M. J., Debate, K. A., Kleeberger, S. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Interstrain+variation+in+murine+aerobic+capacity.">Interstrain variation in murine aerobic capacity.</a> Med. Sci. Sports Exerc. 33 (12), 2053-2057 (2001).</li><li>Turner, M. J., Kleeberger, S. R., Lightfoot, J. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Influence+of+genetic+background+on+daily+running-wheel+activity+differs+with+aging.">Influence of genetic background on daily running-wheel activity differs with aging.</a> Physiol. Genomics. 22 (1), 76-85 (2005).</li><li>Haight, T. J., van der Laan, M. J., Manini, T., Tager, I. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Direct+effects+of+leisure-time+physical+activity+on+walking+speed.">Direct effects of leisure-time physical activity on walking speed.</a> J. Nutr. Health Aging. 17 (8), 666-673 (2013).</li><li>Studenski, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Gait+speed+and+survival+in+older+adults.">Gait speed and survival in older adults.</a> JAMA. 305 (1), 50-58 (2011).</li><li>Jacobsen, K. R., Kalliokoski, O., Teilmann, A. C., Hau, J., Abelson, K. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+effect+of+isoflurane+anaesthesia+and+vasectomy+on+circulating+corticosterone+and+ACTH+in+BALB/c+mice.">The effect of isoflurane anaesthesia and vasectomy on circulating corticosterone and ACTH in BALB/c mice.</a> Gen. Comp. Endocrinol. 179 (3), 406-413 (2012).</li><li>Sellers, T. L., Jaussi, A. W., Yang, H. T., Heninger, R. W., Winder, W. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effect+of+the+exercise-induced+increase+in+glucocorticoids+on+endurance+in+the+rat.">Effect of the exercise-induced increase in glucocorticoids on endurance in the rat.</a> J. Appl. Physiol. 65 (1), 173-178 (1988).</li><li>Cook, M. D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Forced+treadmill+exercise+training+exacerbates+inflammation+and+causes+mortality+while+voluntary+wheel+training+is+protective+in+a+mouse+model+of+colitis.">Forced treadmill exercise training exacerbates inflammation and causes mortality while voluntary wheel training is protective in a mouse model of colitis.</a> Brain Behav. Immun. 33, 46-56 (2013).</li></ol>

作者有没有利益冲突披露。

这里描述的是一种方法，使用电动跑步机不使用电网的冲击，以评估自愿耐力跑在实验室小鼠。这个方法可以揭示之间分线C57BL / 6小鼠的相差在细胞因子IL-15，这又导致在背后运动耐力16,17因子表达的差异表达的差异。在符合原则的"三R"在实验动物科学，这种方法可以作为一种更人性化的选择，或求精，到利用冲击电网8-11被迫行使协议。强迫运动也可以引入心理压力和两个运行参?...

肥胖，胰岛素抵抗和2型糖尿病是会对美国和全球范围内的人口1-4的健康产生深远的影响相互关联的代谢紊乱。耐力运动可预防，以及治疗，这些条件5,6。而且，步态速度和耐力的评估被用于虚弱，肌肉衰减症临床上的诊断测试，以及其它疾病的后果，如慢性阻塞性肺病，在人类对象7。 耐力运动对身体成分和胰岛素敏感性的有益效果背后的生化途径开始被阐明，采用显示增强或运动能力降低8-11的基因或药物基因小鼠。然而，许多这样的研究已经利用装有电网的冲击，迫使老鼠跑8-11电动跑步机。动物谁退出运行是由推运动跑步机皮带上，可提供电动足底电击的网格;为了躲避不良刺激，将小鼠返回到在皮带上运行。这些程序可能会引入心理压力和回避行为的影响的实验参数12的混杂因素。测量耐久的使用光束断在笼车轮运行的装置或定量的其它方法，如动态活动的定量，可通过昼夜周期，焦虑，无意训练，或食物寻求行为12-16的调制被混淆。此外，这些程序需要单个壳体，心理压力的另一个来源为小鼠。因此，需要直接测量运动耐力的不是压力混淆。 为了避免这些问题，我们的实验室已经开发并验证的方法来评估最大运行能力和使用电动跑步机不能球菌持续的运行速度，未受过训练的，天真的小鼠pped与冲击电网。在运行的输送带，其中休克网格通常位于末端的空间，然后变成为小鼠休息的平台，并提供用于该拒绝运行坐下，直到从装置中取出小鼠的地方。小鼠鼓励人类观察者用轻轻拍打或用压舌板，加上灵敏度自愿意愿鼠标的一部分运行感人运行。此方法已被用来量化不同的肌肉衍生的细胞因子白细胞介素15（IL-15）16,17表达基因修饰和控制C57BL / 6小鼠之间的差异在运动耐力。此方法是一种人性化的精致的降低因使用冲击电网的负筋的混杂效应。

<table><tbody><tr><td>Open Rodent Treadmill Exer-3/6</td><td>Columbus Instruments, Columbus OH</td><td>1050RM</td><td>This catalog number is for models without shock grid. Shock grids can be removed manually from older models (Eco 3/6)</td></tr><tr><td>Sani Cloth Germicidal Towlettes</td><td>PDI- Professional Disposables, Inc., Orangeburg, NY</td><td>usually ordered through local facility</td><td>Contains 10% isopropyl alcohol; any equivalent product can be used.</td></tr><tr><td>Tongue depressors</td><td>Any local supplier</td><td></td><td></td></tr><tr><td>Laboratory timer</td><td>Any supplier</td><td></td><td></td></tr><tr><td>IL-15 TG mice*</td><td>JAX, Bar Harbor, ME</td><td>011002</td><td>Murine IL-15 transgene expressed from modified human alpha-skeletal actin promotor with altered signal sequence to facilitate secretion.</td></tr><tr><td>C57BL/6J mice (wild-type)*</td><td>JAX, Bar Harbor, ME</td><td>000664</td><td>Control mice for IL-15 TG</td></tr><tr><td>IL-15 KO mice*</td><td>Taconic Farms, Germantown, NY</td><td>4269-M</td><td>Homozygous IL-15 &quot;knockout&quot; mice on C57BL/6 background</td></tr><tr><td>C57BL/6NTac (wild-type)*</td><td>Taconic Farms, Germantown, NY</td><td>B6-M</td><td>Control mice for IL-15 KO</td></tr><tr><td>*Optional; mouse lines and treatments can be specific to the experimental protocol.</td><td></td><td></td><td></td></tr></tbody></table>

assessment of murine exercise endurance without the use of a shock grid: an alternative to forced exercise

利用实验室小鼠模型，负责耐力运动的代谢好处分子途径开始进行定义。评估小鼠运动耐力的最常用的方法利用强制在电动跑步机上搭载了冲击电网运行。动物谁退出运行是由移动跑步机带压入，可提供电动足底电击的网格;为了躲避不良刺激，将小鼠返回到在皮带上运行。然而，回避行为和心理压力，由于利用冲击装置可以与定量运行的耐力，以及对运动后血清激素和细胞因子水平变乱的测量产生干扰。在这里，我们展示和验证一个精致的方法来衡量在天真的C57BL / 6小鼠的实验室在电动跑步机上跑步的耐力没有利用冲击电网。当小鼠preacclimated到跑步机，它们与步态自行运行速度具体到每个按钮鼠ê。使用冲击网格被替换温和鼓励使用压舌板，加上灵敏度自愿愿意在鼠标的一部分运行人类操作员。清楚的端点用于定量运行时间到用尽每只小鼠被定义，并反映在用尽的行为体征如叉开姿势和呼吸困难。此方法是一种人性化的细化也减少应激对实验参数的混杂影响。

这个程序用于测量运动耐力准确地反映C57BL / 6小鼠的不同菌株而不同的细胞因子IL-15的16,17的表达的分子和代谢分布图。过表达IL-15（IL-15基因小鼠）展览显著运行到用尽倍相比，窝控制增加的转基因小鼠，而缺乏IL-15（IL-15基因敲除小鼠）的小鼠表现出显著达到之前的运行时间缩短耗尽（ 图1A）。已发表 ​​的研究已经表明，肌肉被移向中的IL-15转基因小鼠16的更氧化?...

Watch this Scientific Journal Video about Assessment of Murine Exercise Endurance Without the Use of a Shock Grid: An Alternative to Forced Exercise at JoVE.com

Assessment of Murine Exercise Endurance Without the Use of a Shock Grid: An Alternative to Forced Exercise

A method to assess exercise endurance in laboratory mice without the use of a shock grid is demonstrated. This method is a humane refinement that can decrease the confounding effects of stress on experimental parameters.

小鼠运动耐力的评估没有一个冲击电网的使用:另一种强迫运动

Using laboratory mouse models, the molecular pathways responsible for the metabolic benefits of endurance exercise are beginning to be defined. The most ...

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Universidad San Sebastian

Research

JoVE Journal

Behavior

19.0K 次观看.  VA Puget Sound Health Care System. A method to assess exercise endurance in laboratory mice without the use of a shock grid is demonstrated. This method is a humane refinement that can decrease the confounding effects of stress on experimental parameters.

视频: Assessment of Murine Exercise Endurance Without the Use of a Shock Grid: An Alternative to Forced Exercise

Assessing Functional Performance in the Mdx Mouse Model

Duchenne muscular dystrophy (DMD) is a severe and progressive muscle wasting disorder for which no cure is available. Nevertheless, several potential pharmaceutical compounds and gene therapy approaches have progressed into clinical trials. With improvement in muscle function being the most important end point in these trials, a lot of emphasis has been placed on setting up reliable, reproducible, and easy to perform functional tests to pre clinically assess muscle function, strength, condition, and coordination in the mdx mouse model for DMD. Both invasive and noninvasive tests are available. Tests that do not exacerbate the disease can be used to determine the natural history of the disease and the effects of therapeutic interventions (e.g. forelimb grip strength test, two different hanging tests using either a wire or a grid and rotarod running). Alternatively, forced treadmill running can be used to enhance disease progression and/or assess protective effects of therapeutic interventions on disease pathology. We here describe how to perform these most commonly used functional tests in a reliable and reproducible manner. Using these protocols based on standard operating procedures enables comparison of data between different laboratories.

Assessing Functional Performance in the Mdx Mouse Model

The primary outcome measure in clinical trials for neuromuscular disorders is generally improved muscle function. Therefore, assessing the effect of potential therapeutic compounds on muscle performance pre clinically in mouse models is of great importance. We here describe several functional tests to address this.

评估在功能性能<em&gt; MDX</em&gt;小鼠模型

Duchenne muscular dystrophy (DMD) is a severe and progressive muscle wasting disorder for which no cure is available. Nevertheless, several potential ...

科研

行为学

Getting to Compliance in Forced Exercise in Rodents: A Critical Standard to Evaluate Exercise Impact in Aging-related Disorders and Disease

There is a major increase in the awareness of the positive impact of exercise on improving several disease states with neurobiological basis; these include improving cognitive function and physical performance. As a result, there is an increase in the number of animal studies employing exercise. It is argued that one intrinsic value of forced exercise is that the investigator has control over the factors that can influence the impact of exercise on behavioral outcomes, notably exercise frequency, duration, and intensity of the exercise regimen. However, compliance in forced exercise regimens may be an issue, particularly if potential confounds of employing foot-shock are to be avoided. It is also important to consider that since most cognitive and locomotor impairments strike in the aged individual, determining impact of exercise on these impairments should consider using aged rodents with a highest possible level of compliance to ensure minimal need for test subjects. Here, the pertinent steps and considerations necessary to achieve nearly 100% compliance to treadmill exercise in an aged rodent model will be presented and discussed. Notwithstanding the particular exercise regimen being employed by the investigator, our protocol should be of use to investigators that are particularly interested in the potential impact of forced exercise on aging-related impairments, including aging-related Parkinsonism and Parkinson&#8217;s disease.

Exercise may alleviate behavioral impairments associated with neurodegenerative diseases. Studies of the mechanisms underlying exercise-mediated effects have increased in disease models, but the neurobiological background accompanying these diseases, specifically aging, is likely not considered. Here, we illustrate measures to increase the likelihood of a successful exercise paradigm in aged rats.

让合规的强制锻炼鼠害:一项关键的标准在衰老相关的疾病和疾病评估运动的影响

There is a major increase in the awareness of the positive impact of exercise on improving several disease states with neurobiological basis; these ...

The Treadmill Fatigue Test: A Simple, High-throughput Assay of Fatigue-like Behavior for the Mouse

Fatigue is a prominent symptom in many diseases and disorders and reduces quality of life for many people. The lack of clear pathogenesis and failure of current interventions to adequately treat fatigue in all patients leaves a need for new treatment options. Despite the therapeutic need and importance of preclinical research in helping identify promising novel treatments, few preclinical assays of fatigue are available. Moreover, the most common preclinical assay used to assess fatigue-like behavior, voluntary wheel running, is not suitable for use with some strains of mice, may not be sensitive to drugs that reduce fatigue, and has relatively low throughput. The current protocol describes a novel, non-voluntary preclinical assay of fatigue-like behavior, the treadmill fatigue test, and provides evidence of its efficacy in detecting fatigue-like behavior in mice treated with a chemotherapy drug known to cause fatigue in humans and fatigue-like behavior in animals. This assay may be a beneficial alternative to wheel running, as fatigue-like behavior and potential interventions can be assessed in a greater number of mice over a shorter time frame, thus permitting faster discovery of new therapeutic options.

Fatigue is a common, undertreated and frequently poorly-understood symptom in many diseases and disorders. New preclinical assays of fatigue may help to improve current understanding and future treatment of fatigue. To that end, the current protocol provides a novel means of measuring fatigue-like behavior in the mouse.

跑步机疲劳试验:疲劳类似的行为，为鼠标操作简单，高通量检测

Fatigue is a prominent symptom in many diseases and disorders and reduces quality of life for many people. The lack of clear pathogenesis and failure of ...

A Simple and Low-cost Assay for Measuring Ambulation in Mouse Models of Muscular Dystrophy

Measuring functional outcomes in the treatment of muscular dystrophy is an essential aspect of preclinical testing. The assessment of voluntary ambulation in mouse models is a non-invasive and reproducible activity assay that is directly analogous to measures of patient ambulation such as the 6-minute walk test and related mobility scores. Many common methods for testing mouse ambulation speed and distance are based on the open field test, where an animal&#39;s free movement within an arena is measured over time. One major downside to this approach is that commercial software and equipment for high-resolution motion tracking is expensive and may require transferring mice to specialized facilities for testing. Here, we describe a low-cost, video-based system for measuring mouse ambulation that utilizes free and open-source software. Using this protocol, we demonstrate that voluntary ambulation in the dystrophin-null mdx mouse model for Duchenne muscular dystrophy (DMD) is decreased relative to wild-type mouse activity. In mdx mice expressing the utrophin transgene, these activity deficits are not observed and the total distance traveled is indistinguishable from wild-type mice. This method is effective for measuring changes in voluntary ambulation associated with dystrophic pathology, and provides a versatile platform that can be readily adapted to diverse research settings.

This protocol describes a flexible, low-cost system for measuring mouse ambulation in an open field activity assay. We show that a 6-minute ambulation assay based on this system detects a decrease in voluntary movement in mdx mice, and accurately distinguishes improvement in a muscle-specific rescue of these animals.

一种简便、低成本的肌营养不良小鼠步行模型的测定方法

Measuring functional outcomes in the treatment of muscular dystrophy is an essential aspect of preclinical testing. The assessment of voluntary ambulation ...

Supramaximal Intensity Hypoxic Exercise and Vascular Function Assessment in Mice

Exercise training is an important strategy for maintaining health and preventing many chronic diseases. It is the first line of treatment recommended by international guidelines for patients suffering from cardiovascular diseases, more specifically, lower extremity artery diseases, where the patients' walking capacity is considerably altered, affecting their quality of life. 
Traditionally, both low continuous exercise and interval training have been used. Recently, supramaximal training has also been shown to improve athletes' performances via vascular adaptations, amongst other mechanisms. The combination of this type of training with hypoxia could bring an additional and/or synergic effect, which could be of interest for certain pathologies. Here, we describe how to perform supramaximal intensity training sessions in hypoxia on healthy mice at 150% of their maximal speed, using a motorized treadmill and a hypoxic box. We also show how to dissect the mouse in order to retrieve organs of interest, particularly the pulmonary artery, the abdominal aorta, and the iliac artery. Finally, we show how to perform ex vivo vascular function assessment on the retrieved vessels, using isometric tension studies.

High-intensity training in hypoxia is a protocol that has been proven to induce vascular adaptations potentially beneficial in some patients and to improve athletes&#39; repeated sprint ability. Here, we test the feasibility of training mice using that protocol and identify those vascular adaptations using ex vivo vascular function assessment.

小鼠低血压运动的下位强度及血管功能评估

Exercise training is an important strategy for maintaining health and preventing many chronic diseases. It is the first line of treatment recommended by ...

Short Session High Intensity Interval Training and Treadmill Assessment in Aged Mice

High intensity interval training (HIIT) is emerging as a therapeutic approach to prevent, delay, or ameliorate frailty. In particular short session HIIT, with regimens less than or equal to 10 min is of particular interest as several human studies feature routines as short as a few minutes a couple times a week. However, there is a paucity of animal studies that model the impacts of short session HIIT. Here, we describe a methodology for an individually tailored and progressive short session HIIT regimen of 10 min given 3 days a week for aged mice using an inclined treadmill. Our methodology also includes protocols for treadmill assessment. Mice are initially acclimatized to the treadmill and then given baseline flat and uphill treadmill assessments. Exercise sessions begin with a 3 min warm-up, then three intervals of 1 min at a fast pace, followed by 1 min at an active recovery pace. Following these intervals, the mice are given a final segment that starts at the fast pace and accelerates for 1 min. The HIIT protocol is individually tailored as the speed and intensity for each mouse are determined based upon initial anaerobic assessment scores. Additionally, we detail the conditions for increasing or decreasing the intensity for individual mice depending on performance. Finally, intensity is increased for all mice every two weeks. We previously reported in this protocol enhanced physical performance in aged male mice and here show it also increases treadmill performance in aged female mice. Advantages of our protocol include low administration time (about 15 min per 6 mice, 3 days a week), strategy for individualizing for mice to better model prescribed exercise, and a modular design that allows for the addition or removal of the number and length of intervals to titrate exercise benefits.

Short session (&#8804;10 min) high intensity interval training (HIIT) is emerging as an alternative to longer exercise modalities, yet the shorter variants are rarely modeled in animal studies. Here, we describe a 10 min, 3 day a week, uphill treadmill HIIT protocol that enhances physical performance in male and female aged mice.

老年小鼠短期高强度间隔训练与跑步机评价

High intensity interval training (HIIT) is emerging as a therapeutic approach to prevent, delay, or ameliorate frailty. In particular short session HIIT, ...

猪运动耐力评价

Exercise Test for Evaluation of the Functional Efficacy of the Pig Cardiovascular System

Despite the progress in treatments, cardiovascular diseases are still one of the biggest causes of mortality and morbidity worldwide. Gene therapy-based therapeutic angiogenesis is a promising approach for treating patients with significant symptoms, despite optimal pharmacological therapy and invasive procedures. However, many promising cardiovascular gene therapy techniques have failed to accomplish expectations in clinical trials. One explanation is a mismatch between preclinical and clinical endpoints used to measure efficacy. In animal models, the emphasis has usually been on easily quantifiable endpoints, such as the number and area of the capillary vessels calculated from histological sections. Apart from mortality and morbidity, endpoints in clinical trials are subjective, such as exercise tolerance and quality of life. However, the preclinical and clinical endpoints likely measure different aspects of the applied therapy. Nevertheless, both types of endpoints are required to develop successful therapeutic approaches. In clinics, the main goal is always to alleviate patients' symptoms and improve their prognosis and quality of life. To achieve better predictive data from preclinical studies, endpoint measurements must be better matched to those in clinical studies. Here, we introduce a protocol for a clinically relevant treadmill exercise test in pigs. This study aims to: (1) provide a reliable exercise test in pigs that can be used to evaluate the safety and functional efficacy of gene therapy and other novel therapies, and (2) better match the endpoints between preclinical and clinical studies.

作者聚焦:用于评估猪心血管系统功能功效的运动试验  

The present protocol describes a large animal exercise test model to assess the functional capacity of the cardiovascular system for evaluating the efficiency of new therapies in the preclinical setting. It is comparable to a clinical exercise test.

猪心血管系统功能功效评价的运动试验

Despite the progress in treatments, cardiovascular diseases are still one of the biggest causes of mortality and morbidity worldwide. Gene therapy-based ...

遗传学

A Method to Study the Impact of Chemically-induced Ovarian Failure on Exercise Capacity and Cardiac Adaptation in Mice

The risk of cardiovascular disease (CVD) increases in post-menopausal women, yet, the role of exercise, as a preventative measure for CVD risk in post-menopausal women has not been adequately studied. Accordingly, we investigated the impact of voluntary cage-wheel exercise and forced treadmill exercise on cardiac adaptation in menopausal mice. The most commonly used inducible model for mimicking menopause in women is the ovariectomized (OVX) rodent. However, the OVX model has a few dissimilarities from menopause in humans. In this study, we administered 4-vinylcyclohexene diepoxide (VCD) to female mice, which accelerates ovarian failure as an alternative menopause model to study the impact of exercise in menopausal mice. VCD selectively accelerates the loss of primary and primordial follicles resulting in an endocrine state that closely mimics the natural progression from pre- to peri- to post-menopause in humans. To determine the impact of exercise on exercise capacity and cardiac adaptation in VCD-treated female mice, two methods were used. First, we exposed a group of VCD-treated and untreated mice to a voluntary cage wheel. Second, we used forced treadmill exercise to determine exercise capacity in a separate group VCD-treated and untreated mice measured as a tolerance to exercise intensity and endurance.

Two exercise paradigms were tested on a newly developed chemically induced menopausal mouse model to examine the impact of menopause on exercise capacity and cardiac adaption to exercise.

小鼠运动耐力的评估没有一个冲击电网的使用:另一种强迫运动

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评估在功能性能

让合规的强制锻炼鼠害:一项关键的标准在衰老相关的疾病和疾病评估运动的影响

跑步机疲劳试验:疲劳类似的行为，为鼠标操作简单，高通量检测

一种简便、低成本的肌营养不良小鼠步行模型的测定方法

小鼠低血压运动的下位强度及血管功能评估

老年小鼠短期高强度间隔训练与跑步机评价

猪心血管系统功能功效评价的运动试验

猪心血管系统功能功效评价的运动试验

猪心血管系统功能功效评价的运动试验

一个方法研究的化学诱导卵巢早衰的运动能力和适应心脏的影响在小鼠