Sensory axon targeting is increased by NGF gene therapy within the lesioned adult femoral nerve.
Sensory axon targeting is increased by NGF gene therapy within the lesioned adult femoral nerve.
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DOI：
10.1016/j.expneurol.2009.08.025
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发表时间：
2010-05
影响因子：
5.3
通讯作者：
Smith, George M.
中科院分区：
文献类型：
--
作者：
Hu, Xinhua;Cai, Jie;Yang, Jun;Smith, George M.
关键词：
尽管周围神经再生良好，但轴突经常走错路线，并在受伤后重新支配不适当的远端通路。错误路由最有可能发生在再生轴突做出选择的分支点。在这里，我们表明，通过分叉远端引导分子神经生长因子（NGF）的过度表达，可以提高感觉轴突神经支配的准确性。我们使用股神经作为模型，它包含感觉轴突和运动轴突，它们在母体干中混合，并在远端分离成隐支（SB）和运动支（MB）。母体干的横断导致轴突重新神经支配错误路由至 SB 和 MB。为了增强感觉轴突的靶向性，在损伤一周后，沿着分叉附近的 SB 注射编码 NGF 的重组腺病毒。神经损伤后 3 或 8 周通过逆行追踪评估轴突神经支配的准确性。 NGF 过表达显着增加了 SB 轴突重新神经支配到适当神经分支的准确性，其方式与增强轴突再生无关。这一新发现提供了体内证据，证明神经营养蛋白的梯度表达可用于增强远端外周通路的靶向性，以增加轴突再生到适当的神经分支。
Even though peripheral nerves regenerate well, axons are often misrouted and reinnervate inappropriate distal pathways post-injury. Misrouting most likely occurs at branch points where regenerating axons make choices. Here, we show that the accuracy of sensory axon reinnervation is enhanced by overexpression of the guidance molecule nerve growth factor (NGF) distal to the bifurcation. We used the femoral nerve as model, which contains both sensory and motor axons that intermingle in the parent trunk and distally segregate into the saphenous (SB) and motor branch (MB). Transection of the parent trunk resulted in misrouting of axon reinnervation to SB and MB. To enhance sensory axon targeting, recombinant adenovirus encoding NGF was injected along the SB close to the bifurcation one week post-injury. The accuracy of axon reinnervation was assessed by retrograde tracing at 3 or 8 weeks after nerve injury. NGF overexpression significantly increased the accuracy of SB axon reinnervation to the appropriate nerve branch, in a manner independent of enhancing axon regeneration. This novel finding provides in vivo evidence that gradient expression of neurotrophin can be used to enhance targeting of distal peripheral pathways to increase axon regeneration into the appropriate nerve branch.
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