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钙黏蛋白的上调和重新分布揭示了小鼠华勒氏变性和肌肉去神经支配过程中特定的神经胶质细胞和肌肉细胞表型。

Upregulation and redistribution of cadherins reveal specific glial and muscle cell phenotypes during wallerian degeneration and muscle denervation in the mouse.

作者信息

Padilla F, Marc Mège R, Sobel A, Nicolet M

机构信息

INSERM U 440, Signalisation et Différenciation Cellulaires dans les Systèmes Nerveux et Musculaire, Institut du Fer à Moulin, Paris, France.

出版信息

J Neurosci Res. 1999 Oct 15;58(2):270-83.

Abstract

In the present work, we investigated the expression of cadherin mRNAs in the adult neuromuscular system either under normal conditions or following experimental neurotomy. Cadherin-6, a marker of Schwann cell precursors, was not expressed in the adult peripheral nerve, while M-cadherin, cadherin-11, and N-cadherin were expressed both by glial and conjunctive cells. Moreover, the three transcripts were transiently upregulated in the distal stump of neurotomized sciatic nerve during Wallerian degeneration: N-cadherin was abundant in myelinating Schwann cells during myelin degradation, while M-cadherin and cadherin-11 may be upregulated in proliferating Schwann cells. M-cadherin, cadherin-11, and N-cadherin were also detected in myofibres and endomysium of adult gastrocnemius muscle. Following neurotomy, cadherin-11 was only transiently increased in denervated myofibres, while M-cadherin was increased and sustained for at least 21 days postoperation. In contrast, N-cadherin was not upregulated in denervated myofibres. Thus, we defined here a combination of cadherins expressed in the adult nerve and muscle, and modulated during Wallerian degeneration and muscle denervation. The comparison of the expression pattern of this combination of cadherins to the one previously described during embryonic development shows that chronically denervated Schwann and muscle cells do not reverse to embryonic state (recapitulative hypothesis), but present specific phenotypic features.

摘要

在本研究中,我们调查了正常条件下或实验性神经切断术后成年神经肌肉系统中钙黏蛋白mRNA的表达情况。钙黏蛋白-6是雪旺细胞前体的标志物,在成年外周神经中不表达,而M-钙黏蛋白、钙黏蛋白-11和N-钙黏蛋白在神经胶质细胞和结缔组织细胞中均有表达。此外,在沃勒变性过程中,这三种转录本在神经切断的坐骨神经远端残端中短暂上调:在髓鞘降解过程中,N-钙黏蛋白在形成髓鞘的雪旺细胞中大量存在,而M-钙黏蛋白和钙黏蛋白-11可能在增殖的雪旺细胞中上调。在成年腓肠肌的肌纤维和肌内膜中也检测到了M-钙黏蛋白、钙黏蛋白-11和N-钙黏蛋白。神经切断术后,钙黏蛋白-11仅在失神经支配的肌纤维中短暂增加,而M-钙黏蛋白增加并在术后至少持续21天。相比之下,N-钙黏蛋白在失神经支配的肌纤维中未上调。因此,我们在此定义了成年神经和肌肉中表达的钙黏蛋白组合,以及在沃勒变性和肌肉去神经支配过程中受到调节的组合。将这种钙黏蛋白组合的表达模式与先前在胚胎发育过程中描述的模式进行比较表明,长期失神经支配的雪旺细胞和肌肉细胞不会恢复到胚胎状态(重演假说),而是呈现出特定的表型特征。

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