Striking denervation of neuromuscular junctions without lumbar motoneuron loss in geriatric mouse muscle.
Striking denervation of neuromuscular junctions without lumbar motoneuron loss in geriatric mouse muscle.
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DOI：
10.1371/journal.pone.0028090
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Shavlakadze T
中科院分区：
文献类型：
--
作者：
Chai RJ;Vukovic J;Dunlop S;Grounds MD;Shavlakadze T
与年龄相关的骨骼肌质量和功能逐渐丧失（即肌肉减少症）的原因很复杂。很少有研究描述小鼠的肌肉减少症，尽管该物种是遗传干预和开发肌肉退化药物干预的首选哺乳动物模型。对肌肉减少症相关的神经肌肉变化很重要的一个因素是肌纤维去神经。在这里，我们描述了年轻（3 个月）与老年（29 个月）雌性 C57Bl/6J 小鼠神经肌肉区室的形态。 3 个月和 29 个月时，脊髓腰部 (L1-L5) 运动神经元细胞体的大小或数量没有显着差异。然而，在老年小鼠中，快速伸指长肌（EDL）中完全去神经的神经肌肉接头（NMJ）的百分比和相关的雪旺细胞退化显着增加（约2.5倍），但慢速比目鱼肌中却没有这种情况。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，在 29 个月时，快速 TA 肌肉转变为较快的表型，而慢速比目鱼肌则转变为较慢的表型。总体而言，我们证明了老年小鼠的 NMJ 和肌肉水平发生了复杂的变化，尽管脊髓中的运动神经元细胞体得到了维持。面临的挑战是确定神经肌肉系统的哪些组成部分主要负责 NMJ 和肌肉内的显着变化，以便有选择地针对未来的干预措施来减少肌肉减少症。
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.
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