Name: the treadmill fatigue test: a simple, high-throughput assay of fatigue-like behavior for the mouse
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This research was supported by the Intramural Research Program of the NIH, The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Grant 1Z01 DK011006. We wish to thank Michele Allen for providing technical assistance, Eleni Solomos for editorial assistance, and the NIH veterinary and animal care staff for providing care for the mice used in developing this method.

这个过程被批准为国家糖尿病研究所，消化道和肾脏疾病的动物护理和使用委员会。 1.准备<ol><li>为了允许测试前各小鼠的快速识别，纹身所有小鼠的尾部进行培训，与识别标记检测。 注意:此步骤是可选的。永久性标记或其它识别方法可以用来作为替代纹身。 </li><li>对训练和测试小鼠之前，确保该跑步机是在一个平面上并设置为跑步机的倾斜所需的角度（倾斜的推荐角度:10°，以保持在整个训练和测试一致），并设置电击频率和强度适当的（推荐:2赫兹，1.22 mA）的。 注意:使用的电击应该产生比当由ungloved手指触摸，应以脉动烦恼传递一个轻微的刺痛感没有更多离子（每个震动持续200毫秒）。 </li><li>将屠夫的纸丢球或跑步机下的吸水垫的培训和测试过程中收集的粪便勃利和尿液。 </li><li>将纸从震惊中网格板或在跑步机外壳（ 即透明的塑料盖，涵盖了跑步机车道）的第三个的吸收垫最远。 注意:此步骤是可选的，但将创建一个暗空间，并且可以提供额外的鼓励，以避免在跑步机的下部。 </li><li>如果计划在训练期间使用钢丝刷来提供额外的动力，保证一个是开始训练课之前，一应俱全。 </li><li>确保用于诱导和/或减轻疲劳的任何药物或方法可与可以制备或步骤2.14中进行。 </li></ol> 2.培训小鼠使用跑步机注:训练是必要的，以确保小鼠熟悉跑步机和任务，并进行测试时，可以适当地进行。如果大多数老鼠被训练正在接受频繁的冲击或其他任何训练中表现不佳，更多的培训课程应该执行。在第一天，大多数小鼠会感到震惊几次。通过训练的第二天，将小鼠应该很少使与电网接触。如果老鼠显示训练表现持续欠佳，应该从研究中移除。对于雌性C57BL / 6NCr小鼠，这是一种罕见的发生（小于1％已从由于训练表现不佳研究移除），但应注意的是，其他菌株可以训练过程中执行不同。 <ol><li>与跑步机关闭（和速度设定为0米/分），个别地抬起的尾巴和地点的小鼠到小鼠的跑步机的单独车道小鼠。将每只小鼠在跑步机上后及时打开相应的网格。确保鼠标直接放置Øn中的跑步机带。 注:时间和距离每只小鼠的尾巴持有量应让渡老鼠在跑步机和/或允许老鼠站在一个坚实的平台上（ 例如 ，一个铁丝笼盖前放置跑步机靠近笼子最小化），直到他们在跑步机附近，实验者准备将它们放置在跑步机上。 </li><li>允许小鼠自由地探索跑步1-3分钟或直到每个鼠标已经探索了它的车道和/或从电网获得至少一个冲击。 </li><li>打开在跑步机上并慢慢提高速度，直到它开始移动（约1.5至3.0米/分）。监视所有小鼠，以确保他们开始行走。如果鼠标没有开始走路或向电网震荡行走，准备通过点击鼠标用钢丝刷或尾部发痒介入。 </li><li>缓慢增加跑步机的速度，以8米/分钟。启动一个定时器，并继续监控行为。 </li><li>增加跑步机的速度9米/分钟，在5分钟，10米/分钟，在7分钟，并在10分钟停止跑步机。 </li><li>让老鼠简要探讨跑步机，然后捞出每次回到笼子里。 </li><li>清洁跑步机和电网用酒精和替换跑步机下方的纸或吸水垫。 </li><li>要培养更多的老鼠，重复步骤2.1至2.7。 注:允许酒精来之前，把新的老鼠在跑步机上晾干。 </li><li>在培训的第二天，重复步骤2.1。打开在跑步机上并增加速度以10米/分钟。启动计时器。 注意:跑步机的速度可以快于对训练的第一天增加。 </li><li>增加跑步机的速度为11微米/分钟，在5分钟，12米/分钟，在10分钟，并在15分钟停止跑步机。 </li><li>取出小鼠和他们回到自己的笼子里。 </li><li>清洁跑步机和电网用酒精和替换跑步机下方的纸或吸水垫。要培养更多的老鼠，重复步骤2.9至2.12。 </li><li>以相同的方式与第二日进行的训练额外的天数（3天）。 注:此步骤是可选的，但强烈建议，如果大部分或所有小鼠（的同性和应变）接受培训与任务难度显示屏。小鼠通常可以在步骤3中表现良好时，他们已培训3天（ 即用的训练一个附加天），尽管训练更多或更少的天可以根据在第二训练日它们的性能和的持续时间是适当的步骤2.14。 </li><li>允许至少一整天来传递，其中所述的小鼠都没有接触到跑步机前进至步骤3之前。 注意:使用的任何药物（多个）以诱导和/或缓解疲劳应在该步骤中施用。 注意:此时间周期的长度可以变化，并且用于诱导疲劳和/或测试的干预以减少或消除疲劳。如果在完成训练后，小鼠的测试超过7天，试点研究建议验证所使用的老鼠测试过程中执行。 </li></ol> 3.跑步机疲劳试验注:在该试验中，疲劳样行为被定义为在"疲劳区"花连续5秒。疲劳区域被定义为区域包围休克网格大约为1的车身长度以及网格，自身内的跑步机带的部分。在测试之前，确保划定此区域中的一点是清楚的实验者，诸如通过施加标记到跑步机通道的顶部或侧面。 <ol><li>设置在跑步机速度以12米/分钟。不要启动跑步机。确保电网的冲击被关闭。 </li><li>单独放置到老鼠在跑步机上的单独车道。将每只小鼠在跑步机上后，立即打开对应的网格。 </li><li>同时开始在跑步机和秒表。 注:除了去除小鼠测试期间不要插手满足去除的标准（见步骤3.5）。 </li><li>增加跑步机的速度如表1所示。仔细观察所有小鼠在整个测试。 注:跑步机加快在表1中列出根据从成年雌性C57BL / 6NCr小鼠观察被选定。更高的跑步机的速度可能是适当的大（ 例如 ，远系繁殖的CD-1小鼠）或多个运动的小鼠。 </li><li>如果鼠标停留在5秒连续疲劳区，立即从跑步机移开鼠标并记录时间和距离它跑了。 </li><li>当没有老鼠依然在跑步机上，停止跑步机。清洁跑步机和电网用酒精和替换跑步机下方的纸或吸水垫。 </li><li>要测试其他小鼠，重复步骤3.1至3.6。 注意:此步骤是可选的。 </li></ol>

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The authors have nothing to disclose.

目前的协议将介绍如何使用鼠标跑步机来测量疲劳样行为。这种方法具有超过VWRA，疲劳样行为的共同的临床前试验的几个优点。 VWRA要求小鼠选择与试验装置进行交互。其结果是，小鼠的一些近交系很少与轮16相互作用，并运行这么少，这可能是困难的或不可能识别在活性的疲劳诱导降低。与此相反，在跑步机上的疲劳试验消除了这样的选择，因此，提供的疲劳样行为对不上运行车轮运行...

疲劳影响了各种各样的人，可以显着降低生活质量，并经常有不清楚或不明确的发病机制。癌症有关的疲劳（CRF），例如，是由多数癌症患者经历了接受治疗后的癌症治疗已经完成，并在不存在可检测的癌1的可长期持续。此外，疲劳也是在许多其它疾病和病症，包括慢性疲劳综合征，抑郁症，糖尿病，和纤维肌痛一个突出的症状。幸运的是，那些能够帮助一些人遇到了疲劳非药物干预措施（ 例如 ，运动可降低CRF对一些乳腺癌患者2,3），但许多人仍然缺乏有效的治疗方法。此外，对于CRF现有药物治疗都没有被发现是广泛地说，如果在所有有效的4-7。 尽管治疗需要和缺乏的DRU克的治疗方案，疲劳的临床前试验中的新颖疲劳的治疗缺乏的发现和开发帮助，尤其是在动物模型。一个啮齿类动物的研究疲劳的唯一临床试验的自愿轮运行活动（VWRA）9-15，其中小鼠或其他啮齿动物是给正在运行的车轮和日常运行的活动记录免费进入。在许多研究中，VWRA是疲劳样行为定义（在任VWRA或当前协议），为在所测量的身体活动，实验组的减少的唯一手段，具有疲劳样行为。虽然VWRA可以提供的疲劳样行为的有用纵向量度，这是一个相对低的通量测定法中，在运行的近交小鼠品系16之间变化相当大，并且它要求受试者进行单独圈养，这可能导致在行为和测试性能的变化17-19。其它测定法，如家笼行为监测和分析，也可以提供连续的数据收集和一些系统可以允许被容纳在成对20名受试者。这些测定具有实用性，但也可以是作为检测疲劳样行为的装置不太敏感，并且，象轮运行时，也有低的吞吐量。 在对比VWRA，小鼠跑步机测试不依赖于自愿活性，可在很短的时间框架内完成，允许更高的吞吐量。相比于VWRA，这些测试采用外部激励。具体而言，有通常位于所述移动带的后面，以提供与电击小鼠他们应该停止运行的带电金属网格。除了这个冲击的网格，小鼠可以积极地通过其他多种方法，包括催促，戳，或用一只手，刷子，或其它工具的接触，并在他们引导空气的短喷在跑步机上运行。代替疲劳，鼠标跑步机测试经常用于测量需氧和/或anaerOBIC运动能力21-25。小鼠的动机运行，直到他们是没有能力或不愿意继续在跑步机上作为逃避进一步的电击手段上运行。当小鼠满足疲惫的标准测试，然后结束。在这些协议，以确保小鼠达到真正的生理耗尽，对用尽的标准常常被定义为花连续5秒铺设在休克网格的顶部，并不能继续重复厌恶刺激的面运行。因此，疲劳般的行为可能会在跑步机的典型试验来掩盖由于外部动机和准则结束测试的强烈厌恶的性质。有趣的是，与此相反，使用啮齿类动物跑步机其他许多研究，最近的出版物描述了跑步机的疲劳试验，将其作为社会应激小鼠26的影响的检查的一部分的另一个版本。虽然这一组中使用的方法显着地从CU不同rrent协议（ 即 ，它们采用了单道跑步机需要电击的10秒作为标准来结束他们的测试），他们的研究强调了在开发使用鼠标跑步机一个快速，简单的疲劳试验的效用和利益。 疲劳很可能是由比车轮运行的其他装置，并在日常行为的变化检测的。 CRF使得患者用更少量的肌肉疲劳的感觉筋疲力尽，如肌电图分析，无CRF 27决定的，不是人。此外，主动性降低已注意到并是由几个秤计量人体疲劳28,29测量。因此，疲劳样行为一个有用的临床前试验应健康，疲劳小鼠之间不是生理功能等措施的基础上，积极性不应掩盖下降区别开来。为了实现这一目标，同时避免和VWRA的限制等检测，目前的方法WA■通过调整鼠标平板试验开发。该方法使用一个震动网格作为唯一外部动力，使在跑步机上运行的小鼠。老鼠很快就学会了电网提供了一个厌恶刺激，并从中放置时，在跑步机上，从它运行时，会及时搬走，并保持一定的距离。 当小鼠疲劳，他们花费逐步更多的时间向跑步机，而不是保持速度向前端的后面。因此，在本协议中的标准来测试完成花费在指定的区域疲劳连续5秒（ 即跑步机后，从从震惊电网约一个身体长度，包括震荡网格）。它利用了电网的厌恶性质，而不需要小鼠培训后，收到许多或任何实际的冲击。通过允许小鼠来完成用当前标准而非用尽测试（如上所定义），此方法提供了使用跑步机来测量疲劳样行为，而不是它的最大（或接近最大）生理功能的一种手段。因此，该方法可以提供的疲劳样行为在小鼠中的简单，高通量测定法，并且可以用作或者作为一个独立的或补充措施的疲劳样行为的其他测定法。

<table><tbody><tr><td>Exer 3/6 Animal Treadmill</td><td>Columbus Instruments</td><td>1050-RM Exer-3/6</td><td></td></tr><tr><td>Stopwatch</td><td>Daigger</td><td>EF24490M&amp;nbsp;</td><td></td></tr><tr><td>Wire brush</td><td>Fisher Scientific</td><td>03-572-5</td><td></td></tr><tr><td>Compressed air</td><td>Dust-Off</td><td>FALDSXLPW</td><td></td></tr><tr><td>Absorbent pads</td><td>Daigger</td><td>EF2175CX&amp;nbsp;</td><td></td></tr><tr><td>Butcher paper</td><td>Newell Paper Company</td><td>4620510</td><td></td></tr><tr><td>Alcohol (70%)</td><td>Fisher Scientific</td><td>BP82011</td><td></td></tr></tbody></table>

the treadmill fatigue test: a simple, high-throughput assay of fatigue-like behavior for the mouse

疲劳是在许多疾病和障碍的一个突出的症状，并降低生活质量许多人。缺乏明确的发病机理和电流干预未能在所有患者充分地治疗疲劳叶需要新的治疗选择。尽管治疗需要，并帮助确定有前途的新疗法临床前研究的重要性，疲劳的几个临床前试验可用。此外，用于评估疲劳样行为，自愿车轮运行的最常见的临床前试验中，是不适合与小鼠某些菌株的使用，可能不是减少疲劳的药物敏感，并且具有相对低的吞吐量。当前协议描述了一种新颖的，疲劳样行为，在跑步机上的疲劳试验的非自愿的临床前试验，并提供了其效力的证据在与已知的化疗药物治疗的小鼠检测疲劳样行为引起疲劳在人类和疲劳在灵魂般的行为LS。该测定可以是有益的替代车轮运行，如疲劳样行为和潜在的干预可以在较短的时间帧的小鼠更大数目进行评估，因此允许的新的治疗选择更快发现。

该协议允许在使用跑步机的小鼠被测定疲劳样行为。在本节中给出的数据是通过训练和测试3个独立使用当前的协议（不包括图1A及1C）的小鼠组得到的。为了诱导疲劳，5-氟尿嘧啶（5-FU），已知的细胞毒性化疗药物引起人类30和小鼠-10,13-疲劳样行为疲劳，施用。中所有的数据来自成年雌性C57BL / 6NCr小鼠。小鼠9-10（ 图1和2）<...

Watch this Scientific Journal Video about The Treadmill Fatigue Test: A Simple, High-throughput Assay of Fatigue-like Behavior for the Mouse at JoVE.com

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

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 ...

the-treadmill-fatigue-test-simple-high-throughput-assay-fatigue-like

Universidad San Sebastian

Research

JoVE Journal

Behavior

18.5K 次观看.  National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. 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.

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

A Mouse Model of Fatigue Induced by Peripheral Irradiation

Cancer-related fatigue (CRF) is a distressing and costly condition that often affects patients receiving cancer treatments, including radiation therapy. Here we describe a method using targeted peripheral irradiation to induce fatigue-like behavior in mice. With appropriate shielding, the irradiation targets the lower abdominal/pelvic region of the mouse, sparing the brain, in an effort to model radiation treatment received by individuals with pelvic cancers. We deliver an irradiation dose that is sufficient to induce fatigue-like behavior in mice, measured by voluntary wheel-running activity (VWRA), without causing obvious morbidity. Since wheel running is a normal, voluntary behavior in mice, its use should have little confounding effect on other behavioral tests or biological measures. Hence, wheel running can be used as a feasible outcome measure in understanding the behavioral and biological correlates of fatigue. CRF is a complex condition with frequent comorbidities, and likely has causes related both to cancer and its various treatments. The methods described in this paper are useful for investigating radiation-induced changes that contribute to the development of CRF and, more generally, to explore the biological networks that can explain the development and persistence of a peripherally-triggered but centrally-driven behavior like fatigue.

We describe a method using targeted peripheral irradiation to induce fatigue-like behavior in mice. The selected non-lethal irradiation dose leads to a week-long reduction in voluntary wheel-running activity.

疲劳的小鼠模型的外围照射引起

Cancer-related fatigue (CRF) is a distressing and costly condition that often affects patients receiving cancer treatments, including radiation therapy. ...

科研

癌症研究

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 ...

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 ...

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

Using laboratory mouse models, the molecular pathways responsible for the metabolic benefits of endurance exercise are beginning to be defined. The most common method for assessing exercise endurance in mice utilizes forced running on a motorized treadmill equipped with a shock grid. Animals who quit running are pushed by the moving treadmill belt onto a grid that delivers an electric foot shock; to escape the negative stimulus, the mice return to running on the belt. However, avoidance behavior and psychological stress due to use of a shock apparatus can interfere with quantitation of running endurance, as well as confound measurements of postexercise serum hormone and cytokine levels. Here, we demonstrate and validate a refined method to measure running endurance in na&#239;ve C57BL/6 laboratory mice on a motorized treadmill without utilizing a shock grid. When mice are preacclimated to the treadmill, they run voluntarily with gait speeds specific to each mouse. Use of the shock grid is replaced by gentle encouragement by a human operator using a tongue depressor, coupled with sensitivity to the voluntary willingness to run on the part of the mouse. Clear endpoints for quantifying running time-to-exhaustion for each mouse are defined and reflected in behavioral signs of exhaustion such as splayed posture and labored breathing. This method is a humane refinement which also decreases the confounding effects of stress on experimental parameters.

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 ...

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, ...

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.

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

The risk of cardiovascular disease (CVD) increases in post-menopausal women, yet, the role of exercise, as a preventative measure for CVD risk in ...

医学

Measuring Skeletal Muscle Thermogenesis in Mice and Rats

Skeletal muscle thermogenesis provides a potential avenue for better understanding metabolic homeostasis and the mechanisms underlying energy expenditure. Surprisingly little evidence is available to link the neural, myocellular, and molecular mechanisms of thermogenesis directly to measurable changes in muscle temperature. This paper describes a method in which temperature transponders are utilized to retrieve direct measurements of mouse and rat skeletal muscle temperature.
Remote transponders are surgically implanted within the muscle of mice and rats, and the animals are given time to recover. Mice and rats must then be repeatedly habituated to the testing environment and procedure. Changes in muscle temperature are measured in response to pharmacological or contextual stimuli in the home cage. Muscle temperature can also be measured during prescribed physical activity (i.e., treadmill walking at a constant speed) to factor out changes in activity as contributors to the changes in muscle temperature induced by these stimuli.
This method has been successfully used to elucidate mechanisms underlying muscle thermogenic control at the level of the brain, sympathetic nervous system, and skeletal muscle. Provided are demonstrations of this success using predator odor (PO; ferret odor) as a contextual stimulus and injections of oxytocin (Oxt) as a pharmacological stimulus, where predator odor induces muscle thermogenesis, and Oxt suppresses muscle temperature. Thus, these datasets display the efficacy of this method in detecting rapid changes in muscle temperature.

Mice and rats are surgically implanted with remote temperature transponders and then habituated to the testing environment and procedure. Changes in muscle temperature are measured in response to pharmacological or contextual stimuli in the home cage or during prescribed physical activity (i.e., treadmill walking at a constant speed).

测量小鼠和大鼠的骨骼肌产热

Skeletal muscle thermogenesis provides a potential avenue for better understanding metabolic homeostasis and the mechanisms underlying energy expenditure. ...

Visualization of MG53-mediated Cell Membrane Repair Using in vivo and in vitro Systems

Repair of acute injury to the cell membrane is an elemental process of normal cellular physiology, and defective membrane repair has been linked to many degenerative human diseases. The recent discovery of MG53 as a key component of the membrane resealing machinery allows for a better molecular understanding of the basic biology of tissue repair, as well as for potential translational applications in regenerative medicine. Here we detail the experimental protocols for exploring the in vivo function of MG53 in repair of muscle injury using treadmill exercise protocols on mouse models, for testing the ex vivo membrane repair capacity by measuring dye entry into isolated muscle fibers, and for monitoring the dynamic process of MG53-mediated vesicle trafficking and cell membrane repair in cultured cells using live cell confocal microscopy.

Visualization of MG53-mediated Cell Membrane Repair Using in vivo and in vitro Systems

Described here are protocols used to visualize the dynamic process of MG53-mediated cell membrane repair in whole animals and at the cellular level. These methods can be applied to investigate the cell biology of plasma membrane resealing and regenerative medicine.

MG53介导的细胞膜使用维修的可视化在体内在体外系统

Repair of acute injury to the cell membrane is an elemental process of normal cellular physiology, and defective membrane repair has been linked to many ...

生物学

A Rat Model of Central Fatigue Using a Modified Multiple Platform Method

In this article, we introduced a rat model of central fatigue using the modified multiple platform method (MMPM). The Multiple Platform box was designed as a water tank with narrow platforms on the bottom. The model rats were put into the tank and stood on the platforms for 14 h (18:00 - 8:00) per day for a consecutive 21 days, with a blank control group set for contrast. At the end of modeling, rats in the model group showed an obvious fatigued appearance. To assess the model, we performed several behavioral tests, including the open field test (OFT), the elevated plus maze (EPM) test, and the exhaustive swimming (ES) test. The results showed that anxiety, spatial cognition impairment, poor muscle performance, and declined voluntary activity presented in model rats confirm the diagnosis of&#160;central fatigue. Changes of the central neurotransmitters also verified the result. In conclusion, the model successfully simulated central fatigue, and future study with the model may help reveal the pathological mechanism of the disease.

Here, we present a protocol to introduce a rat model of central fatigue using the modified multiple platform method (MMPM).

基于改进多平台法的大鼠中心疲劳模型

In this article, we introduced a rat model of central fatigue using the modified multiple platform method (MMPM). The Multiple Platform box was designed ...

神经科学

Real-Time Electrocardiogram Monitoring During Treadmill Training in Mice

Regular physical exercise is a major contributor to cardiovascular health, influencing various metabolic as well as electrophysiological processes. However, in certain cardiac diseases such as inherited arrhythmia syndromes, e.g., arrhythmogenic cardiomyopathy (ACM) or myocarditis, physical exercise may have negative effects on the heart leading to a proarrhythmogenic substrate production. Currently, the underlying molecular mechanisms of exercise-related proarrhythmogenic remodeling are largely unknown, thus it remains unclear which frequency, duration, and intensity of exercise can be considered safe in the context of disease(s).
The proposed method allows to study proarrhythmic/antiarrhythmic effects of physical exercise by combining treadmill training with real-time monitoring of the ECG. Implantable telemetry devices are used to continuously record the ECG of freely moving mice over a period of up to 3 months both at rest and during treadmill training. Data acquisition software with its analysis modules is used to analyze basic ECG parameters such as heart rate, P wave duration, PR interval, QRS interval, or QT duration at rest, during and after training. Furthermore, heart rate variability (HRV) parameters and occurrence of arrhythmias are evaluated. In brief, this manuscript describes a step-by-step approach to experimentally explore exercise induced effects on cardiac electrophysiology, including potential proarrhythmogenic remodeling in mouse models.

Electrocardiogram (ECG) is the key variable to understanding cardiac electrophysiology. Physical exercise has beneficial effects but may also be harmful in the context of cardiovascular diseases. This manuscript provides a method of recording real-time ECG during exercise, which can serve to investigate its effects on cardiac electrophysiology in mice.

小鼠跑步机训练期间的实时心电图监测

Regular physical exercise is a major contributor to cardiovascular health, influencing various metabolic as well as electrophysiological processes. ...