Neurotrophin selectivity in organizing topographic regeneration of nociceptive afferents.
Neurotrophin selectivity in organizing topographic regeneration of nociceptive afferents.
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DOI：
10.1016/j.expneurol.2015.06.007
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发表时间：
2015-09
影响因子：
5.3
通讯作者：
Smith, George M.
中科院分区：
文献类型：
--
作者：
Kelamangalath, Lakshmi;Tang, Xiaoqing;Bezik, Kathleen;Sterling, Noelle;Son, Young-Jin;Smith, George M.
神经营养因子代表了一些最好的候选人，以加强再生。在目前的研究中，我们调查的artemin，胶质源性神经营养因子（GDNF）家族的成员，感觉轴突再生后，腰椎背根损伤，并比较这些效果后观察到的神经生长因子或GDNF表达在大鼠脊髓。与以前发表的数据不同，artemin在脊髓或DRG内表达时未能诱导大直径有髓感觉传入神经再生。然而，artemin或NGF诱导降钙素基因相关肽阳性（CGRP+）轴突再生时，只在脊髓内表达。因此，artemin或NGF增强恢复只有伤害性行为，并表现出cFos分布类似的拓扑结构再生轴突。Artemin和GDNF信号传导需要在与信号传导受体cRet结合之前与不同的共受体（分别为GFRα3或GFRα1）结合。大约70%的DRG神经元表达cRet，但只有35%表达任一共受体。为了增强artemin诱导的再生，我们将artemin与GFRα3或GDNF共表达。artemin和GFRα3的共表达仅轻微增强IB 4+非肽能伤害性轴突的再生，但不增强有髓鞘轴突的再生。有趣的是，这种共表达也破坏了artemin产生拓扑靶向的能力，并导致深背层内cFos免疫反应性显著增加。这项研究未能证明青蒿素诱导的有髓轴突再生，即使与GFR-α3共表达，这只会促进错误的再生。
Neurotrophins represent some of the best candidates to enhance regeneration. In the current study, we investigated the effects of artemin, a member of the glial derived neurotrophic factor (GDNF) family, on sensory axon regeneration following a lumbar dorsal root injury and compared these effects with that observed after either NGF or GDNF expression in the rat spinal cord. Unlike previously published data, artemin failed to induce regeneration of large-diameter myelinated sensory afferents when expressed within either the spinal cord or DRG. However, artemin or NGF induced regeneration of calcitonin gene related peptide positive (CGRP+) axons only when expressed within the spinal cord. Accordingly, artemin or NGF enhanced recovery of only nociceptive behavior and showed a cFos distribution similar to the topography of regenerating axons. Artemin and GDNF signaling requires binding to different co-receptors (GFRα3 or GFRα1, respectively) prior to binding to the signaling receptor, cRet. Approximately 70% of DRG neurons express cRet, but only 35% express either co-receptor. To enhance artemin-induced regeneration, we co-expressed artemin with either GFRα3 or GDNF. Co-expression of artemin and GFRα3 only slightly enhanced regeneration of IB4+ non-peptidergic nociceptive axons, but not myelinated axons. Interestingly, this co-expression also disrupted the ability of artemin to produce topographic targeting and lead to significant increases in cFos immunoreactivity within the deep dorsal laminae. This study failed to demonstrate artemin-induced regeneration of myelinated axons, even with co-expression of GFR-α3, which only promoted mistargeted regeneration.
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影响因子：
4.6
作者：
Hancock, Melissa L.;Nowakowski, Dan W.;Flanagan, John G.
通讯作者：
Flanagan, John G.
DOI：
10.1073/pnas.1003287107
发表时间：
2010-06-22
影响因子：
11.1
作者：
Harvey, Pamela;Gong, BangJian;Frank, Eric
通讯作者：
Frank, Eric
DOI：
10.1073/pnas.84.18.6596
发表时间：
1987-09-01
影响因子：
11.1
作者：
DIAMOND, J;COUGHLIN, M;VISHEAU, B
通讯作者：
VISHEAU, B
影响因子：
2.5
作者：
DOUCETTE, R;DIAMOND, J
通讯作者：
DIAMOND, J
影响因子：
2.5
作者：
Hannila, SS;Kawaja, MD
通讯作者：
Kawaja, MD