School of Anatomy and Human Biology, The University of Western Australia, Perth, Western Australia, Australia.
PLoS One. 2011;6(12):e28090. doi: 10.1371/journal.pone.0028090. Epub 2011 Dec 2.
Reasons for the progressive age-related loss of skeletal muscle mass and function, namely sarcopenia, are complex. Few studies describe sarcopenia in mice, although this species is the mammalian model of choice for genetic intervention and development of pharmaceutical interventions for muscle degeneration. One factor, important to sarcopenia-associated neuromuscular change, is myofibre denervation. Here we describe the morphology of the neuromuscular compartment in young (3 month) compared to geriatric (29 month) old female C57Bl/6J mice. There was no significant difference in the size or number of motoneuron cell bodies at the lumbar level (L1-L5) of the spinal cord at 3 and 29 months. However, in geriatric mice, there was a striking increase (by ∼2.5 fold) in the percentage of fully denervated neuromuscular junctions (NMJs) and associated deterioration of Schwann cells in fast extensor digitorum longus (EDL), but not in slow soleus muscles. There were also distinct changes in myofibre composition of lower limb muscles (tibialis anterior (TA) and soleus) with a shift at 29 months to a faster phenotype in fast TA muscle and to a slower phenotype in slow soleus muscle. Overall, we demonstrate complex changes at the NMJ and muscle levels in geriatric mice that occur despite the maintenance of motoneuron cell bodies in the spinal cord. The challenge is to identify which components of the neuromuscular system are primarily responsible for the marked changes within the NMJ and muscle, in order to selectively target future interventions to reduce sarcopenia.
骨骼肌质量和功能进行性年龄相关丧失的原因，即肌肉减少症，十分复杂。尽管该物种是遗传干预和肌肉退行性病变药物干预发展的首选哺乳动物模型，但很少有研究描述小鼠的肌肉减少症。一个重要的因素是肌纤维去神经支配，这与肌肉减少症相关的神经肌肉变化有关。在这里，我们描述了年轻（3 个月）与老年（29 个月）雌性 C57Bl/6J 小鼠相比，其运动神经元细胞体在脊髓腰段（L1-L5）的形态。3 个月和 29 个月时，脊髓腰段（L1-L5）的运动神经元细胞体的大小或数量没有显著差异。然而，在老年小鼠中，完全去神经支配的神经肌肉接头（NMJ）的百分比显著增加（增加约 2.5 倍），并且快速伸趾长肌（EDL）中的施万细胞明显恶化，但在慢速比目鱼肌中则不然。下肢肌肉（胫骨前肌（TA）和比目鱼肌）的肌纤维组成也发生了明显变化，29 个月时，快速 TA 肌肉向更快的表型转变，而慢速比目鱼肌向更慢的表型转变。总体而言，我们在老年小鼠中证明了 NMJ 和肌肉水平的复杂变化，尽管脊髓中的运动神经元细胞体保持不变。挑战在于确定神经肌肉系统的哪些成分主要负责 NMJ 和肌肉内的明显变化，以便有针对性地进行未来的干预以减少肌肉减少症。
