Schwann Cells in Neuromuscular Junction Formation and Maintenance
Schwann Cells in Neuromuscular Junction Formation and Maintenance
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DOI：
10.1523/jneurosci.0174-16.2016
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发表时间：
2016-09-21
影响因子：
5.3
通讯作者：
Mei, Lin
中科院分区：
文献类型：
--
作者：
Barik, Arnab;Li, Lei;Mei, Lin
神经肌肉接头（NMJ）是由运动神经末梢、接头后肌膜和覆盖神经-肌肉接触的末端许旺细胞（TSC）形成的三联突触。NMJ的形成需要三个不同组成部分之间的密切沟通。与神经-肌肉相互作用不同的是，它已经被很好地表征，对SC在NMJ形成和维持中的作用知之甚少。我们发现，小鼠的SC导致神经末梢的预模式AChRs。在E8.5处对SC进行分级（即，在E13.5时，SC对神经丛AChR簇的影响很小，这表明SC可能不是神经丛所必需的。SC消融在E12.5，时间膈神经接近肌纤维，导致更小，更少的神经诱导的AChR集群;然而，SC消融在E15.5减少AChR集群的大小，但集群密度没有影响，表明SC参与AChR集群成熟。当SC在E15.5消融时，微型终板电位振幅而不是频率降低，表明突触后改变可能发生在突触前缺陷之前。最后，在P30消融SC，NMJ成熟后，导致NMJ断裂和神经肌肉传递缺陷。消融后3d微终板电位波幅降低，6d微终板电位波幅和频率均降低。总之，这些结果表明，SC不仅需要NMJ的形成，但也是必要的，其维护和突触后功能和结构似乎是更敏感的SC消融。
The neuromuscular junction (NMJ) is a tripartite synapse that is formed by motor nerve terminals, postjunctional muscle membranes, and terminal Schwann cells (TSCs) that cover the nerve-muscle contact. NMJ formation requires intimate communications among the three different components. Unlike nerve-muscle interaction, which has been well characterized, less is known about the role of SCs in NMJ formation and maintenance. We show that SCs in mice lead nerve terminals to prepatterned AChRs. Ablating SCs at E8.5 (i.e., prior nerve arrival at the clusters) had little effect on aneural AChR clusters at E13.5, suggesting that SCs may not be necessary for aneural clusters. SC ablation at E12.5, a time when phrenic nerves approach muscle fibers, resulted in smaller and fewer nerve-induced AChR clusters; however, SC ablation at E15.5 reduced AChR cluster size but had no effect on cluster density, suggesting that SCs are involved in AChR cluster maturation. Miniature endplate potential amplitude, but not frequency, was reduced when SCs were ablated at E15.5, suggesting that postsynaptic alterations may occur ahead of presynaptic deficits. Finally, ablation of SCs at P30, after NMJ maturation, led to NMJ fragmentation and neuromuscular transmission deficits. Miniature endplate potential amplitude was reduced 3 d after SC ablation, but both amplitude and frequency were reduced 6 d after. Together, these results indicate that SCs are not only required for NMJ formation, but also necessary for its maintenance; and postsynaptic function and structure appeared to be more sensitive to SC ablation.