Assessing spinal axon regeneration and sprouting in Nogo-, MAG-, and OMgp-deficient mice.

Assessing spinal axon regeneration and sprouting in Nogo-, MAG-, and OMgp-deficient mice.
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DOI:
10.1016/j.neuron.2010.05.002
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发表时间:
2010-06-10
期刊:
影响因子:
16.2
通讯作者:
Zheng, Binhai
Zheng, Binhai
中科院分区:
医学1区
文献类型:
--
作者:
Lee, Jae K.;Geoffroy, Cedric G.;Chan, Andrea F.;Tolentino, Kristine E.;Crawford, Michael J.;Leal, Marisa A.;Kang, Brian;Zheng, Binhai

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成人中枢神经系统(CNS)轴突再生能力有限的一个核心假设是髓鞘衍生的轴突生长抑制剂的存在,然而,其作用仍然知之甚少。我们已经进行了全面的遗传分析的三个主要的髓鞘抑制剂,Nogo,MAG和OMgp,在损伤诱导的轴突生长,包括未受伤的轴突的补偿发芽和受伤的轴突再生。虽然删除任何一种抑制剂在小鼠中增强发芽的皮质脊髓或raphespinal神经轴突,既没有相关的行为改善,也没有协同效应删除所有三种抑制剂。此外,三重突变小鼠未能表现出脊髓损伤后轴突束的再生增强。我们的数据表明,虽然Nogo,MAG和OMgp可以调节轴突发芽,他们不发挥中枢神经系统轴突再生失败的核心作用。
A central hypothesis for the limited capacity for adult central nervous system (CNS) axons to regenerate is the presence of myelin-derived axon growth inhibitors, the role of which, however, remains poorly understood. We have conducted a comprehensive genetic analysis of the three major myelin inhibitors, Nogo, MAG and OMgp, in injury-induced axonal growth, including compensatory sprouting of uninjured axons and regeneration of injured axons. While deleting any one inhibitor in mice enhanced sprouting of corticospinal or raphespinal serotonergic axons, there was neither associated behavioral improvement nor a synergistic effect of deleting all three inhibitors. Furthermore, triple mutant mice failed to exhibit enhanced regeneration of either axonal tract after spinal cord injury. Our data indicate that while Nogo, MAG and OMgp may modulate axon sprouting, they do not play a central role in CNS axon regeneration failure.
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