Li Shuxin, Kim Ji-Eun, Budel Stephane, Hampton Thomas G, Strittmatter Stephen M
Department of Neurology, Yale University School of Medicine, PO Box 208018, New Haven, CT 06510, USA.
Mol Cell Neurosci. 2005 May;29(1):26-39. doi: 10.1016/j.mcn.2004.12.008.
Axon growth after spinal injury is thought to be limited in part by myelin-derived proteins that act via the Nogo-66 Receptor (NgR). To test this hypothesis, we sought to study recovery from spinal cord injury (SCI) after inhibiting NgR transgenically with a soluble function-blocking NgR fragment. Glial fibrillary acidic protein (gfap) gene regulatory elements were used to generate mice that secrete NgR(310)ecto from astrocytes. After mid-thoracic dorsal over-hemisection injury, gfap::ngr(310)ecto mice exhibit enhanced raphespinal and corticospinal axonal sprouting into the lumbar spinal cord. Recovery of locomotion is improved in the gfap::ngr(310)ecto mice. These data indicate that the NgR ligands, Nogo-66, MAG, and OMgp, play a role in limiting axonal growth in the injured adult CNS and that NgR(310)ecto might provide a therapeutic means to promote recovery from SCI.
脊髓损伤后轴突生长被认为部分受髓磷脂衍生蛋白的限制,这些蛋白通过Nogo-66受体(NgR)发挥作用。为了验证这一假设,我们试图研究通过转基因抑制NgR,使用可溶性功能阻断NgR片段后脊髓损伤(SCI)的恢复情况。利用胶质纤维酸性蛋白(gfap)基因调控元件培育出能从星形胶质细胞分泌NgR(310)胞外区的小鼠。在胸中段背侧半横断损伤后,gfap::ngr(310)胞外区小鼠的中缝脊髓和皮质脊髓轴突向腰脊髓的芽生增强。gfap::ngr(310)胞外区小鼠的运动功能恢复得到改善。这些数据表明,NgR配体Nogo-66、MAG和OMgp在限制成年中枢神经系统损伤后轴突生长中起作用,并且NgR(310)胞外区可能为促进SCI恢复提供一种治疗手段。