Application of Rho antagonist to neuronal cell bodies promotes neurite growth in compartmented cultures and regeneration of retinal ganglion cell axons in the optic nerve of adult rats
Application of Rho antagonist to neuronal cell bodies promotes neurite growth in compartmented cultures and regeneration of retinal ganglion cell axons in the optic nerve of adult rats
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DOI：
10.1523/jneurosci.3931-04.2005
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发表时间：
2005-02-02
影响因子：
5.3
通讯作者：
McKerracher, L
中科院分区：
文献类型：
--
作者：
Bertrand, J;Winton, MJ;McKerracher, L
Rho的失活促进了抑制底物上的神经突生长和轴突再生。在这里，我们比较了神经细胞体或受损轴突在体外和体内用细胞渗透性Rho拮抗剂（C3-07）处理时的轴突生长情况。在区室培养的神经元中，将C3-07应用于细胞体或远端轴突均可促进髓鞘相关糖蛋白底物上的轴突生长。体内注射C3-07可促进视神经微挤压损伤后视网膜神经节细胞（RGC）轴突的再生。C3-07的延迟应用促进了RGC在病变瘢痕上的生长。C3-07应用后1周内完全阻止RGC细胞死亡。为了研究Rho失活促进RGC生长的机制，我们研究了慢轴突运输。在轴突切开后，观察到细胞骨架蛋白的缓慢运输减少，但Rho的失活并未增加缓慢轴突运输率。总之，我们的研究结果表明，在细胞体上应用Rho拮抗剂具有神经保护作用，克服了生长抑制，但不能完全激活rgc的活性生长。
Inactivation of Rho promotes neurite growth on inhibitory substrates and axon regeneration in vivo. Here, we compared axon growth when neuronal cell bodies or injured axons were treated with a cell-permeable Rho antagonist (C3-07) in vitro and in vivo. In neurons plated in compartmented cultures, application of C3-07 to either cell bodies or distal axons promoted axonal growth on myelin-associated glycoprotein substrates. In vivo, an injection of C3-07 into the eye promoted regeneration of retinal ganglion cell (RGC) axons in the optic nerve after microcrush lesion. Delayed application of C3-07 promoted RGC growth across the lesion scar. Application of C3-07 completely prevented RGC cell death for 1 week after axotomy. To investigate the mechanism by which Rho inactivation promotes RGC growth, we studied slow axonal transport. Reduction in slow transport of cytoskeletal proteins was observed after axotomy, but inactivation of Rho did not increase slow axonal transport rates. Together, our results indicate that application of a Rho antagonist at the cell body is neuroprotective and overcomes growth inhibition but does not fully prime RGCs for active growth.