Quinlan Katharina A, Kajtaz Elma, Ciolino Jody D, Imhoff-Manuel Rebecca D, Tresch Matthew C, Heckman Charles J, Tysseling Vicki M
Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Department of Preventative Medicine, Northwestern University, Chicago, IL, USA.
J Physiol. 2017 Aug 1;595(15):5387-5400. doi: 10.1113/JP274170. Epub 2017 Jul 5.
The present study demonstrates that electromyograms (EMGs) obtained during locomotor activity in mice were effective for identification of early physiological markers of amyotrophic lateral sclerosis (ALS). These measures could be used to evaluate therapeutic intervention strategies in animal models of ALS. Several parameters of locomotor activity were shifted early in the disease time course in SOD1G93A mice, especially when the treadmill was inclined, including intermuscular phase, burst skew and amplitude of the locomotor bursts. The results of the present study indicate that early compensatory changes may be taking place within the neural network controlling locomotor activity, including spinal interneurons. Locomotor EMGs could have potential use as a clinical diagnostic tool.
To improve our understanding of early disease mechanisms and to identify reliable biomarkers of amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease, we measured electromyogram (EMG) activity in hind limb muscles of SOD1G93A mice. By contrast to clinical diagnostic measures using EMGs, which are performed on quiescent patients, we monitored activity during treadmill running aiming to detect presymptomatic changes in motor patterning. Chronic EMG electrodes were implanted into vastus lateralis, biceps femoris posterior, lateral gastrocnemius and tibialis anterior in mice from postnatal day 55 to 100 and the results obtained were assessed using linear mixed models. We evaluated differences in parameters related to EMG amplitude (peak and area) and timing (phase and skew, a measure of burst shape) when animals ran on level and inclined treadmills. There were significant changes in both the timing of activity and the amplitude of EMG bursts in SOD1G93A mice. Significant differences between wild-type and SOD1G93A mice were mainly observed when animals locomoted on inclined treadmills. All muscles had significant effects of mutation that were independent of age. These novel results indicate (i) locomotor EMG activity might be an early measure of disease onset; (ii) alterations in locomotor patterning may reflect changes in neuronal drive and compensation at the network level including altered activity of spinal interneurons; and (iii) the increased power output necessary on an inclined treadmill was important in revealing altered activity in SOD1G93A mice.
本研究表明，在小鼠运动活动期间获得的肌电图（EMG）对于识别肌萎缩侧索硬化症（ALS）的早期生理标志物是有效的。这些测量方法可用于评估ALS动物模型中的治疗干预策略。在SOD1G93A小鼠的疾病进程早期，运动活动的几个参数发生了变化，尤其是当跑步机倾斜时，包括肌间相位、爆发偏斜和运动爆发的幅度。本研究结果表明，在控制运动活动的神经网络（包括脊髓中间神经元）内可能正在发生早期代偿性变化。运动肌电图可能有作为临床诊断工具的潜在用途。
为了增进我们对早期疾病机制的理解并识别肌萎缩侧索硬化症（ALS，一种进行性神经退行性疾病）的可靠生物标志物，我们测量了SOD1G93A小鼠后肢肌肉的肌电图（EMG）活动。与对静息患者进行的使用EMG的临床诊断措施不同，我们监测了跑步机跑步期间的活动，旨在检测运动模式的症状前变化。将慢性EMG电极植入出生后第55天至100天小鼠的股外侧肌、股二头肌后部、腓肠外侧肌和胫骨前肌，并使用线性混合模型评估获得的结果。当动物在水平和倾斜的跑步机上跑步时，我们评估了与EMG幅度（峰值和面积）和时间（相位和偏斜，一种爆发形状的测量）相关的参数差异。SOD1G93A小鼠的活动时间和EMG爆发幅度均有显著变化。野生型和SOD1G93A小鼠之间的显著差异主要在动物在倾斜跑步机上运动时观察到。所有肌肉都有独立于年龄的显著突变效应。这些新结果表明：（i）运动EMG活动可能是疾病发作的早期指标；（ii）运动模式的改变可能反映了神经元驱动和网络水平的代偿变化，包括脊髓中间神经元活动的改变；（iii）在倾斜跑步机上所需的增加的功率输出对于揭示SOD1G93A小鼠的活动改变很重要。
