Inhibition of MAPK ERK impairs axonal regeneration without an effect on neuronal loss after nerve injury
Inhibition of MAPK ERK impairs axonal regeneration without an effect on neuronal loss after nerve injury
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DOI：
10.1179/174313209x380883
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发表时间：
2009-12-01
影响因子：
1.9
通讯作者：
Chentanez, V.
中科院分区：
文献类型：
--
作者：
Agthong, S.;Koonam, J.;Chentanez, V.
细胞外信号调节蛋白激酶(ERK)是丝裂原活化蛋白激酶家族中的一员，已被证明在体外介导了多种神经营养因子促进轴突生长的作用。此外，在体内，ERK在神经损伤后的初级感觉神经元和相关的神经胶质细胞中被激活。目的：探讨ERK抑制对轴索损伤后轴突再生和神经元丢失的影响。方法：采用单侧坐骨神经挤压损伤模型，通过腹腔注射U0126 300 mg·kg~(-1)·d~(-1)，连续2周抑制ERK的表达。结果：在损伤的坐骨神经中，ERK被激活，而抑制剂显著降低了ERK的活性。而L4/L5脊神经节中未见ERK的激活。形态分析显示两组神经元丢失程度相似。此外，抑制剂组的平均再生距离低于对照组。结论：ERK在创伤后神经再生中起重要作用，而不是感觉神经元的丢失。[Neurol Res 2009；31：1068-1074]
Activation of extracellular signal-regulated protein kinase (ERK), a member of the mitogen-activated protein kinase family, has been shown to mediate neurite outgrowth-promoting effects of various neurotrophic factors in vitro. Moreover, in vivo, ERK is activated in the primary sensory neurons and associated glial cells after nerve injury. However, the precise role of ERK in nerve regeneration remains unclear.Objective: This work was aimed to investigate the effects of ERK inhibition on axonal regeneration and neuronal loss after axotomy.Methods: Unilateral sciatic nerve crush was performed, and inhibition of ERK was achieved by intraperitoneal injection of 300 mu g kg(-1) day(-1) of u0126 for 2 weeks in the inhibitor group. For the control group, only the vehicle was given with the same schedule.Results: ERK was activated in the crushed sciatic nerve, and this was significantly reduced by the inhibitor. In contrast, there was no activation of ERK in the L4/L5 spinal ganglia. Morphological analysis revealed the similar extent of neuronal loss in the two groups. In addition, the mean regeneration distance in the inhibitor group was lower than that of the control group.Conclusion: These results suggest the crucial role of ERK in nerve regeneration but not sensory neuronal loss after trauma. [Neurol Res 2009; 31: 1068-1074]