Neonatal partial denervation results in nodal but not terminal sprouting and a decrease in efficacy of remaining neuromuscular junctions in rat soleus muscle
Neonatal partial denervation results in nodal but not terminal sprouting and a decrease in efficacy of remaining neuromuscular junctions in rat soleus muscle
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DOI：
10.1523/jneurosci.19-20-08931.1999
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发表时间：
1999-10-15
影响因子：
5.3
通讯作者：
Thompson, WJ
中科院分区：
文献类型：
--
作者：
Lubischer, JL;Thompson, WJ
成熟的运动神经元通过发芽来重新支配去神经纤维来对其目标肌肉的部分去神经做出反应，从而在面对因损伤或疾病引起的运动神经元损失时保持肌肉力量。然而，新生儿运动神经元不会扩张以支配更多的肌纤维。目前的工作旨在了解运动神经元对部分去神经反应的这种发育变化。有人认为，新生儿运动单位的尺寸不能增加，因为它们已经达到最大尺寸（大约是成年时的五倍）。我们通过证明在出生后第 14 天 (P14) 部分去神经后，当运动单位减小到成年尺寸时，运动神经元仍然没有发芽来重新支配与成年时一样多的纤维，从而排除了这种解释。相反，我们发现了支持涉及终末雪旺细胞的另一种解释的证据。新生儿（但不是成人）肌肉部分去神经后，去神经终板的终末雪旺细胞会发生凋亡。我们发现部分去神经支配的新生儿肌肉不存在终末（而非节点）出芽。这一发现表明，先前报道的终末雪旺细胞可将终末芽引导至成人肌肉中去神经支配的终板，这对于终末芽的形成和生长是必需的。此外，P14 的部分去神经严重削弱了剩余的、未受伤的突触，这表明新生儿运动神经元可能在附近纤维去神经后撤回末端。这些发现对解释先前关于突触消除的研究具有重要意义，并提供了对部分去神经后年轻运动单位扩张失败的见解。
Mature motoneurons respond to partial denervation of their target muscle by sprouting to reinnervate denervated fibers, thus maintaining muscle strength in the face of motoneuronal loss caused by injury or disease. Neonatal motoneurons, however, do not expand to innervate more muscle fibers. The present work seeks to understand this developmental change in motoneuron response to partial denervation. It has been suggested that neonatal motor units cannot increase in size because they are already at their maximum size (approximately five times larger than in adulthood). We ruled out this explanation by showing that after partial denervation on postnatal day 14 (P14), when motor units have decreased to their adult size, motoneurons still did not sprout to reinnervate as many fibers as in adulthood. Instead, we found evidence supporting an alternative explanation involving terminal Schwann cells. After partial denervation of neonatal (but not adult) muscles, terminal Schwann cells at denervated endplates undergo apoptosis. We found that terminal (but not nodal) sprouting was absent in partially denervated neonatal muscles. This finding suggests that terminal Schwann cells, previously reported to guide terminal sprouts to denervated endplates in adult muscles, are necessary for the formation and growth of terminal sprouts. Moreover, partial denervation on P14 severely weakened the remaining, uninjured synapses, suggesting that neonatal motoneurons may withdraw terminals after the denervation of nearby fibers. These findings have implications for the interpretation of previous studies on synapse elimination and offer insight into the failure of young motor units to expand after partial denervation.