Influence of laminin‐2 on Schwann cell–axon interactions

Influence of laminin‐2 on Schwann cell–axon interactions
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DOI:
10.1002/1098-1136(200011)32:2
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发表时间:
2000-11
期刊:
影响因子:
6.2
通讯作者:
Y. Uziyel;S. Hall;James Cohen
Y. Uziyel;S. Hall;James Cohen
中科院分区:
医学1区
文献类型:
--
作者:
Y. Uziyel;S. Hall;James Cohen

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dy/dy小鼠患有一种由层粘连蛋白α2-链蛋白(肌肉和雪旺细胞基底层的主要成分)大量减少引起的肌营养不良症。本文研究了层粘连蛋白α2缺乏对神经损伤后不同时间段的体内雪旺细胞-轴突相互作用的影响,以及体外神经元和雪旺细胞共培养中的雪旺细胞-轴突相互作用。在未压碎的dy/dy坐骨神经中观察到的异常雪旺细胞-轴突协会的形态学谱在再生过程中被重演:再生轴突的髓鞘形成与未受影响的小鼠的过程相比被延迟,并且在dy/dy远端神经残端中形成的相对较少的髓鞘通常是未压实的。在体外,从成人dy/dy坐骨神经分离的雪旺细胞可预见地不能表达可检测的层粘连蛋白α2-链,并显示出不寻常的多极形态。在dy/dy雪旺细胞上生长的背根神经节神经元的神经突分支,无论是终末分支的数量还是分支的复杂性,都比神经元与来自未受影响的同窝仔的雪旺细胞共培养时所观察到的范围要小得多,但这种效应被外源性层粘连蛋白-2逆转。我们的研究结果有力地支持了这样一种观点,即层粘连蛋白-2对于建立和/或维持正常和再生神经中的雪旺细胞-轴突相互作用至关重要。GLIA 32:109-121,2000.© 2000 Wiley利斯公司
The dy/dy mouse suffers from a form of muscular dystrophy caused by a substantial reduction in laminin α2‐chain protein, a major component of both muscle and Schwann cell basal laminae. This article examines the effect of laminin α2 deficiency on Schwann cell–axon interactions both in vivo at varying intervals after nerve crush, and in vitro, in cocultures of neurons and Schwann cells. The morphological spectrum of aberrant Schwann cell–axon associations seen in uncrushed dy/dy sciatic nerves was recapitulated during regeneration: myelination of regenerating axons was delayed compared with the process in unaffected mice and the relatively few myelin sheaths which were formed in dy/dy distal nerve stumps were often uncompacted. In vitro, Schwann cells dissociated from adult dy/dy sciatic nerves predictably failed to express detectable laminin α2‐chain and displayed an unusual multipolar morphology. Branching of neurites, in terms both of numbers of terminal branches and of complexity of branching, from dorsal root ganglia neurons grown on dy/dy Schwann cells, was significantly less extensive than that seen when neurons were cocultured with Schwann cells from unaffected littermates, but this effect was reversed by exogenous laminin‐2. Our results lend strong support to the view that laminin‐2 is essential for establishing and/or maintaining Schwann cell–axon interactions, in normal and in regenerating nerves. GLIA 32:109–121, 2000. © 2000 Wiley‐Liss, Inc.