Sciatic nerve injury in adult rats causes distinct changes in the central projections of sensory neurons expressing different glial cell line-derived neurotrophic factor family receptors.

Sciatic nerve injury in adult rats causes distinct changes in the central projections of sensory neurons expressing different glial cell line-derived neurotrophic factor family receptors.
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DOI:
10.1002/cne.22378
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发表时间:
2010-08-01
影响因子:
2.5
通讯作者:
Osborne, Peregrine B.
Osborne, Peregrine B.
中科院分区:
医学3区
文献类型:
--
作者:
Keast, Janet R.;Forrest, Shelley L.;Osborne, Peregrine B.

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成年大鼠背神经节(DRG)中的大多数无髓小神经元表达胶质细胞系源性神经营养因子(GDNF)靶向的一种或多种共受体neurturin和artemin(分别为GFRα1、GFRα2和GFRα3)。这些GDNF家族配体(GFLs)的功能尚未完全阐明,但最近的证据表明GFLs可以在神经损伤和外周伤害感受器敏化后的感觉神经元再生中起作用。在这项研究中,我们使用免疫组织化学方法来确定每个GFL靶向的DRG神经元在坐骨神经损伤后是否发生变化。我们比较了完全坐骨神经切断和慢性压迫模型,发现每种损伤引起的变化模式大致相似。在腰髓中,L1-6背角神经元GFRα1免疫反应性(IR)广泛增加。GFRα3-IR也升高,但范围较局限。相反,GFRα2-IR在浅表背角斑片中降低,并且这种损失在横断损伤后更广泛。降钙素基因相关肽-IR在两种损伤后均未检测到变化。对双标记L5 DRG切片的分析表明,损伤对GFRα1-和GFRα3-IR的主要影响是增加有髓和无髓神经元中的表达。相反,通过荧光强度分析,在DRG中未检测到GFRα2-IR基础表达的变化,GFRα2-IR神经元中存在少量但显著的减少。我们的研究结果表明,GDNF,neurturin或artemin靶向的DRG神经元群体,以及外源性GFLs的作用可以在周围神经损伤后发生显着变化。
Most small unmyelinated neurons in adult rat dorsal ganglia (DRG) express one or more of the co-receptors targeted by glial cell line-derived neurotrophic factor (GDNF), neurturin and artemin (GFRα1, GFRα2 and GFRα3 respectively). The function of these GDNF family ligands (GFLs) is not fully elucidated but recent evidence suggests GFLs could function in sensory neuron regeneration after nerve injury and peripheral nociceptor sensitisation. In this study, we used immunohistochemistry to determine if the DRG neurons targeted by each GFL change after sciatic nerve injury. We compared complete sciatic nerve transection and the chronic constriction model and found the pattern of changes incurred by each injury was broadly similar. In lumbar spinal cord, there was a widespread increase in neuronal GFRα1 immunoreactivity (IR) in the L1-6 dorsal horn. GFRα3-IR also increased but in a more restricted area. In contrast, GFRα2-IR decreased in patches of superficial dorsal horn and this loss was more extensive after transection injury. No change in calcitonin gene-related peptide-IR was detected after either injury. Analysis of double-immunolabelled L5 DRG sections suggested the main effect of injury on GFRα1- and GFRα3-IR was to increase expression in both myelinated and unmyelinated neurons. In contrast, no change in basal expression of GFRα2-IR was detected in DRG by analysis of fluorescence intensity and there was a small but significant reduction in GFRα2-IR neurons. Our results suggest the DRG neuronal populations targeted by GDNF, neurturin or artemin, and the effect of exogenous GFLs could change significantly after a peripheral nerve injury.
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