Local down-regulation of myelin-associated glycoprotein permits axonal sprouting with chronic nerve compression injury
Local down-regulation of myelin-associated glycoprotein permits axonal sprouting with chronic nerve compression injury
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DOI：
10.1016/j.expneurol.2006.02.134
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发表时间：
2006-08-01
影响因子：
5.3
通讯作者：
Steward, Oswald
中科院分区：
文献类型：
--
作者：
Gupta, Ranjan;Rummler, Laura S.;Steward, Oswald
慢性神经压迫（CNC）损伤以不同的空间和时间模式诱导强大的雪旺细胞增殖，这伴随着损伤区域中小的无髓鞘轴突数量的增加。这些结果表明，这种局部的雪旺细胞增殖可能会导致局部轴突发芽。在这里，我们使用定量电子显微镜技术来定义这种发芽反应的性质，并探讨是否本地发芽是在响应髓鞘相关糖蛋白（MAG）的表达下调增殖雪旺细胞。轴突发芽观察到没有证据的华勒变性的外部区域的CNC损伤的神经与雷马克束在该区域内的损伤明显增加。免疫标记的戏弄神经纤维和蛋白质印迹分析的神经从CNC损伤的动物揭示了一个局部下调MAG蛋白的损伤区内。此外，在CNC模型创建时神经内局部递送纯化的MAG蛋白消除了轴突发芽反应。这些数据表明CNC损伤触发轴突发芽，并表明继发于CNC损伤的外周神经内MAG的局部下调是发芽反应的关键信号。(c)2006年爱思唯尔公司All rights reserved.
Chronic nerve compression (CNC) injuries induce a robust Schwann cell proliferation in a distinct spatial and temporal pattern, which is accompanied by an increase in the number of small un-myelinated axons in the area of the injury. These findings suggest that this local proliferation of Schwann cells may induce local axonal sprouting. Here, we use quantitative electron microscopic techniques to define the nature of this sprouting response, and explore whether the local sprouting is in response to down-regulation of expression of myelin-associated glycoprotein (MAG) by proliferating Schwann cells. Axonal sprouting was observed without evidence of Wallerian degeneration in the outer region of CNC-injured nerves with a noticeable increase in Remak bundles within this region of injury. Immunolabeling of teased nerve fibers and Western blot analysis of nerves from CNC-injured animals revealed a local down-regulation of MAG protein within the zone of injury. Moreover, local delivery of purified MAG protein intraneurally at the time of CNC model creation abrogates the axonal sprouting response. These data demonstrate that CNC injury triggers axonal sprouting and suggests that a local down-regulation of MAG within the peripheral nerve secondary to CNC injury is the critical signal for the sprouting response. (c) 2006 Elsevier Inc. All rights reserved.