Department of Molecular, Cellular, and Integrative Physiology, University of California, Los Angeles, CA, 90034, USA.
Department of Human Genetics, David Geffen School of Medicine at UCLA, 695 Charles E. Young Drive South, Los Angeles, CA, 90095, USA.
Sci Rep. 2022 Sep 30;12(1):16428. doi: 10.1038/s41598-022-20665-y.
Grip strength is a valuable preclinical assay to study muscle physiology in disease and aging by directly determining changes in muscle force generation in active laboratory mice. Existing methods to statistically evaluate grip strength, however, have limitations in the power and scope of the physiological features that are assessed. We therefore designed a microcontroller whose serial measure of resistance-based force enables the simultaneous readout of (1) peak grip strength, (2) force profile (the non-linear progress of force exerted throughout a standard grip strength trial), and (3) cumulative force profile (the integral of force with respect to time of a single grip strength trial). We hypothesized that muscle pathologies of different etiologies have distinct effects on these parameters. To test this, we used our apparatus to assess the three muscle parameters in mice with impaired muscle function resulting from surgically induced peripheral pain, genetic peripheral neuropathy, adverse muscle effects induced by statin drug, and metabolic alterations induced by a high-fat diet. Both surgically induced peripheral nerve injury and statin-associated muscle damage diminished grip strength and force profile, without affecting cumulative force profile. Conversely, genetic peripheral neuropathy resulting from lipin 1 deficiency led to a marked reduction to all three parameters. A chronic high-fat diet led to reduced grip strength and force profile when normalized to body weight. In high-fat fed mice that were exerted aerobically and allowed to recover for 30 min, male mice exhibited impaired force profile parameters, which female mice were more resilient. Thus, simultaneous analysis of peak grip strength, force profile and cumulative force profile distinguishes the muscle impairments that result from distinct perturbations and may reflect distinct motor unit recruitment strategies.
握力是一种有价值的临床前检测方法,可通过直接测量活跃实验小鼠肌肉力量的变化来研究疾病和衰老中的肌肉生理学。然而,现有的握力统计评估方法在评估的生理特征的功率和范围方面存在局限性。因此,我们设计了一种微控制器,其基于电阻的力的串行测量能够同时读取(1)最大握力,(2)力曲线(在标准握力试验中力的非线性进展)和(3)累积力曲线(单个握力试验中力相对于时间的积分)。我们假设不同病因的肌肉病理学对这些参数有不同的影响。为了验证这一点,我们使用我们的设备评估了三种肌肉参数,这些参数在由于手术引起的周围疼痛、遗传周围神经病变、他汀类药物引起的不良肌肉效应以及高脂肪饮食引起的代谢改变而导致肌肉功能受损的小鼠中。手术引起的周围神经损伤和他汀类药物相关的肌肉损伤均降低了握力和力曲线,而不影响累积力曲线。相反,由于脂肪酶 1 缺乏引起的遗传周围神经病变导致所有三个参数明显降低。慢性高脂肪饮食导致握力和力曲线降低,但按体重归一化后则不受影响。在进行有氧运动并允许恢复 30 分钟的高脂肪喂养小鼠中,雄性小鼠表现出力曲线参数受损,而雌性小鼠则更有弹性。因此,同时分析最大握力、力曲线和累积力曲线可区分由不同干扰引起的肌肉损伤,并可能反映不同的运动单位募集策略。