Demyelination can proceed independently of axonal degradation during Wallerian degeneration in Wlds mice
Demyelination can proceed independently of axonal degradation during Wallerian degeneration in Wlds mice
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Wlds 小鼠沃勒变性过程中脱髓鞘的发生可以独立于轴突降解
DOI：
10.1111/j.1460-9568.2011.07783.x
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发表时间：
2011
影响因子：
3.4
通讯作者：
Toshiyuki Araki
中科院分区：
文献类型：
--
作者：
Hitomi Takada;Toshiyuki Araki
周围神经损伤诱导轴突变性和脱髓鞘，其统称为沃勒变性。一般认为轴突变性是随后脱髓鞘过程的触发因素，例如髓鞘破坏和许旺细胞的去分化，但轴突变性后脱髓鞘初始阶段发生的事件的详细顺序仍不清楚。在这里，我们进行了形态学分析损伤的坐骨神经的wldsmice，一种自然发生的突变小鼠，其中沃勒变性显示出显着的延迟。wldsmutant小鼠的缓慢沃勒变性表型将使我们能够剖析在脱髓鞘的初始阶段发生的事件。电镜超微结构分析表明，髓鞘破坏的初始过程中被激活的wldsmice损伤的神经，即使他们表现出形态学上完全保护轴突对神经损伤。我们还发现，一些完整的轴突完全脱髓鞘在变性神经的wldsmice。此外，我们观察到，即使轴突在形态上保持完整，髓鞘形成的雪旺细胞的去分化也逐渐进行。这些数据表明，在损伤的周围神经脱髓鞘的起始和进展是，至少部分，独立的轴突变性。
Peripheral nerve injury induces axonal degeneration and demyelination, which are collectively referred to as Wallerian degeneration. It is generally assumed that axonal degeneration is a trigger for the subsequent demyelination processes such as myelin destruction and de‐differentiation of Schwann cells, but the detailed sequence of events that occurs during this initial phase of demyelination following axonal degeneration remains unclear. Here we performed a morphological analysis of injured sciatic nerves ofwldsmice, a naturally occurring mutant mouse in which Wallerian degeneration shows a significant delay. The slow Wallerian degerenation phenotype of thewldsmutant mice would enable us to dissect the events that take place during the initial phase of demyelination. Ultrastrucural analysis using electron microscopy showed that the initial process of myelin destruction was activated in injured nerves ofwldsmice even though they exhibit morphologically complete protection of axons against nerve injury. We also found that some intact axons were completely demyelinated in degenerating nerves ofwldsmice. Furthermore, we observed that de‐differentiation of myelinating Schwann cells gradually proceeded even though the axons remained morphologically intact. These data suggest that initiation and progression of demyelination in injured peripheral nerves is, at least in part, independent of axonal degeneration.