Axonal regeneration after sciatic nerve lesion is delayed but complete in GFAP- and vimentin-deficient mice.

Axonal regeneration after sciatic nerve lesion is delayed but complete in GFAP- and vimentin-deficient mice.
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DOI:
10.1371/journal.pone.0079395
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Cullheim S
Cullheim S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Berg A;Zelano J;Pekna M;Wilhelmsson U;Pekny M;Cullheim S

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运动神经元的外周轴突切断引发损伤轴突远端的沃勒变性,随后轴突再生。在中枢,轴突切断诱导脊髓中受损运动神经元表面的突触丢失(突触剥离)。在病变部位,反应性施万细胞为长出的轴突提供营养支持和指导。突触剥离的机制仍然难以捉摸,但反应性星形胶质细胞和小胶质细胞似乎是重要的,在这个过程中。我们研究了缺乏中间丝(纳米丝)蛋白胶质细胞酸性蛋白(GFAP)和波形蛋白的小鼠坐骨神经损伤后运动神经元的轴突再生和突触剥离,这些蛋白在反应性星形胶质细胞和雪旺细胞中上调。坐骨神经切断后7天,损伤的运动神经元胞体上的突触密度的超微结构分析显示,更多的剩余的终扣覆盖在GFAP-/-Vim-/-小鼠损伤的胞体。GFAP-/-Vim-/-小鼠坐骨神经损伤后,腓肠肌肌纤维上再神经支配的运动终板的比例在损伤后13天减少,轴突再生和功能恢复延迟但完全。因此,胶质细胞中GFAP和波形蛋白的缺乏似乎不会影响外周运动神经元损伤后的结果,但可能对反应动力学有重要影响。
Peripheral axotomy of motoneurons triggers Wallerian degeneration of injured axons distal to the lesion, followed by axon regeneration. Centrally, axotomy induces loss of synapses (synaptic stripping) from the surface of lesioned motoneurons in the spinal cord. At the lesion site, reactive Schwann cells provide trophic support and guidance for outgrowing axons. The mechanisms of synaptic stripping remain elusive, but reactive astrocytes and microglia appear to be important in this process. We studied axonal regeneration and synaptic stripping of motoneurons after a sciatic nerve lesion in mice lacking the intermediate filament (nanofilament) proteins glial fibrillary acidic protein (GFAP) and vimentin, which are upregulated in reactive astrocytes and Schwann cells. Seven days after sciatic nerve transection, ultrastructural analysis of synaptic density on the somata of injured motoneurons revealed more remaining boutons covering injured somata in GFAP–/–Vim–/– mice. After sciatic nerve crush in GFAP–/–Vim–/– mice, the fraction of reinnervated motor endplates on muscle fibers of the gastrocnemius muscle was reduced 13 days after the injury, and axonal regeneration and functional recovery were delayed but complete. Thus, the absence of GFAP and vimentin in glial cells does not seem to affect the outcome after peripheral motoneuron injury but may have an important effect on the response dynamics.
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