Blockade of Nogo receptor ligands promotes functional regeneration of sensory axons after dorsal root crush.
Blockade of Nogo receptor ligands promotes functional regeneration of sensory axons after dorsal root crush.
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DOI：
10.1523/jneurosci.5885-08.2009
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发表时间：
2009-05-13
期刊：
影响因子：
--
通讯作者：
Frank E
中科院分区：
文献类型：
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作者：
Harvey PA;Lee DH;Qian F;Weinreb PH;Frank E
中枢神经系统内轴突再生的一个主要障碍是与髓鞘相关的多种抑制因子的存在。其中有三种因子与Nogo受体NgR结合，NgR在轴突上表达。给予NGR或NGR配体的外源性阻滞剂可促进脊髓半横断后下行轴突投射的再生。通过检测背根挤压伤后特定类型的感觉神经轴突进入脊髓的生长情况，可以对中枢神经系统的再生进行更详细的分析。在这项研究中，我们评估了给予与所有三种NGR配体结合并阻断的NGR的可溶肽片段是否可以促进成年大鼠臂背根挤压后的再生。脑室内注射SNGR一个月后，有髓感觉神经轴突广泛再生到脊髓背侧的白质和灰质，但无髓感觉神经传入不能再生。脊髓灰质细胞外微电极记录显示，随着感觉神经轴突向脊髓的解剖生长，失神经区域的突触功能逐渐恢复。这些积极的突触反应与前肢使用的显著改善有关，通过爪子偏好、爪子对触觉刺激的缩回和抓取能力进行评估。这些结果表明，SNGR可能是恢复感觉神经根损伤后感觉功能的一种潜在疗法。
A major impediment for regeneration of axons within the central nervous system is the presence of multiple inhibitory factors associated with myelin. Three of these factors bind to the Nogo receptor, NgR, which is expressed on axons. Administration of exogenous blockers of NgR or NgR ligands promotes the regeneration of descending axonal projections after spinal cord hemisection. A more detailed analysis of CNS regeneration can be made by examining the growth of specific classes of sensory axons into the spinal cord after dorsal root crush injury . In this study, we assessed whether administration of a soluble peptide fragment of the NgR that binds to and blocks all three NgR ligands can promote regeneration after brachial dorsal root crush in adult rats. Intraventricular infusion of sNgR for one month results in extensive regrowth of myelinated sensory axons into the white and gray matter of the dorsal spinal cord, but unmyelinated sensory afferents do not regenerate. In concert with the anatomical growth of sensory axons into the cord, there is a gradual restoration of synaptic function in the denervated region, as revealed by extracellular microelectrode recordings from the spinal gray matter in response to stimulation of peripheral nerves. These positive synaptic responses are correlated with substantial improvements in use of the forelimb, as assessed by paw preference, paw withdrawal to tactile stimuli and the ability to grasp. These results suggest that sNgR may be a potential therapy for restoring sensory function following injuries to sensory roots.