Nogo-66 receptor prevents raphespinal and rubrospinal axon regeneration and limits functional recovery from spinal cord injury
Nogo-66 receptor prevents raphespinal and rubrospinal axon regeneration and limits functional recovery from spinal cord injury
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DOI：
10.1016/j.neuron.2004.10.015
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发表时间：
2004-10-28
期刊：
影响因子：
16.2
通讯作者：
Strittmatter, SM
中科院分区：
文献类型：
--
作者：
Kim, JE;Liu, BP;Strittmatter, SM
成年哺乳动物CNS损伤后的轴突再生部分受限于CNS髓鞘中的三种抑制性蛋白：Nogo-A、MAG和OMgp。所有这三种蛋白质都与Nogo-66受体（NgR）结合以抑制体外轴突生长。为了探索NgR对髓鞘抑制剂的反应和对成年CNS中轴突生长的限制的必要性，我们产生了ngr（-1-）小鼠。缺乏NgR的小鼠是可行的，但表现出活动减退和运动障碍。缺乏NgR的DRG神经元不结合Nogo-66，并且它们的生长锥不被Nogo-66破坏。在脊髓背侧半切或完全横断后，ngr（-1-）小鼠的运动功能恢复得到改善。虽然在缺乏NgR的小鼠中皮质脊髓纤维不再生，但确实发生了一些中缝脊髓和红核脊髓纤维的再生。因此，NgR是部分负责限制某些纤维系统在成年中枢神经系统的再生。
Axon regeneration after injury to the adult mammalian CNS is limited in part by three inhibitory proteins in CNS myelin: Nogo-A, MAG, and OMgp. All three of these proteins bind to a Nogo-66 receptor (NgR) to inhibit axonal outgrowth in vitro. To explore the necessity of NgR for responses to myelin inhibitors and for restriction of axonal growth in the adult CNS, we generated ngr(-1-) mice. Mice lacking NgR are viable but display hypoactivity and motor impairment. DRG neurons lacking NgR do not bind Nogo-66, and their growth cones are not collapsed by Nogo-66. Recovery of motor function after dorsal hemisection or complete transection of the spinal cord is improved in the ngr(-1-) mice. While corticospinal fibers do not regenerate in mice lacking NgR, regeneration of some raphespinal and rubrospinal fibers does occur. Thus, NgR is partially responsible for limiting the regeneration of certain fiber systems in the adult CNS.