The neurotrophin receptor p75NTR in Schwann cells is implicated in remyelination and motor recovery after peripheral nerve injury

The neurotrophin receptor p75NTR in Schwann cells is implicated in remyelination and motor recovery after peripheral nerve injury
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DOI:
10.1002/glia.20533
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发表时间:
2007-08-15
期刊:
影响因子:
6.2
通讯作者:
Hosokawa, Ko
Hosokawa, Ko
中科院分区:
医学1区
文献类型:
--
作者:
Tomita, Koichi;Kubo, Tateki;Hosokawa, Ko

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P75(NTR)神经营养素受体(p75(NTR))在神经系统再生中的作用仍存在争议。这种争议的部分原因可能是p75(NTR)在神经细胞和神经胶质细胞类型中都有表达,并且在每个群体中可能具有非常不同的甚至相互矛盾的作用。为了阐明p75(NTR)在周围神经损伤后雪旺细胞髓鞘形成过程中的体内作用,我们建立了p75(NTR)缺陷雪旺细胞裸鼠移植动物模型。我们对坐骨神经损伤后的功能、组织学和电生理恢复进行了定量评估,并与P75(NTR)(+1+)雪旺细胞移植动物进行了比较。伤后710周,p75(NTR)(-/-)雪旺细胞移植组动物运动功能恢复明显低于p75(NTR)(+/+)雪旺细胞移植组动物。P75(NTR)(-/-)雪旺细胞移植动物在伤后6周和10周,运动神经元逆行标记神经元数量减少,髓鞘减少。在损伤后10周,NTR组P75(NTR)(-/-)Schwann区轴突直径的放射状生长也受到损害。细胞移植动物。损伤后10周的髓鞘蛋白含量和神经传导速度的测定反映了这些结果。综上所述,雪旺细胞中p75(NTR)的表达对再生髓鞘过程是重要的,损伤后的运动恢复由于轴突生长、再生髓鞘和轴突口径的放射状生长受损而受损。(C)2007年Wiley-Liss,Inc.
The function of the p75(NTR) neurotrophin receptor (p75(NTR)) in nervous system regeneration is still controversial. Part of that controversy may be due to the fact that p75(NTR) is expressed by both neuronal and glial cell types and may have very distinct and even contradictory roles in each population. In this study, to elucidate the in vivo function of p75(NTR) in Schwann cells during remyelination after peripheral nerve injury, we established a new animal model for p75(NTR)-deficient Schwann cell transplantation in nude mice. We performed quantitative assessments of the functional, histological, and electro physiological recovery after sciatic nerve injury, and compared them with those of the P75(NTR)(+1+) Schwann cell transplanted animals. At 710 weeks after injury, the motor recovery in the p75(NTR)(-/-) Schwann cell transplanted animals was significantly impaired compared with that in the p75(NTR)(+/+) Schwann cell transplanted animals. The lower number of the retrogradely labeled motoneurons and the hypomyelination in the p75(NTR)(-/-) Schwann cell transplanted animals were evident at 6 and 10 weeks after injury. At 10 weeks after injury, the radial growth in the axon caliber was also impaired in NTR the P75(NTR)(-/-) Schwann. cell transplanted animals. Measurement of the amount of myelin proteins and the nerve conduction velocity at 10 weeks after injury reflected these results. In summary, the p75(NTR) expression in Schwann cells is important for remyelination process, and the motor recovery after injury is impaired due to impaired axonal growth, remyelination, and radial growth in the axon calibers. (C) 2007 Wiley-Liss, Inc.