Nogo-66 receptor prevents raphespinal and rubrospinal axon regeneration and limits functional recovery from spinal cord injury.
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(-/-) 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(-/-) 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.
Kim
Ji-Eun
JE
Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA.
Liu
Betty P
BP
Park
James H
JH
Strittmatter
Stephen M
SM
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D001369:Axons / Q000502:physiology*; D001522:Behavior, Animal; D015152:Blotting, Northern / Q000379:methods; D015139:Blotting, Southern / Q000379:methods; D001921:Brain / Q000473:pathology; D002452:Cell Count / Q000379:methods; D002478:Cells, Cultured; D003001:Cloning, Molecular / Q000379:methods; D055233:Cornified Envelope Proline-Rich Proteins; D003891:Desipramine / Q000494:pharmacology; D004195:Disease Models, Animal; D019054:Evoked Potentials, Motor / Q000502:physiology; D005260:Female; D058851:GPI-Linked Proteins; D005727:Ganglia, Spinal / Q000166:cytology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005947:Glucose / Q000031:analogs & derivatives* / Q000494:pharmacology; D020439:Growth Cones / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D009186:Myelin Sheath / Q000378:metabolism; D018992:Myelin-Associated Glycoprotein; D009416:Nerve Regeneration; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D010742:Phospholipid Ethers / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism; D011712:Pyramidal Tracts / Q000503:physiopathology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020127:Recovery of Function / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism; D018490:Serotonin Agents / Q000494:pharmacology; D013116:Spinal Cord / Q000378:metabolism / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000235:genetics / Q000503:physiopathology* / Q000517:prevention & control; D013997:Time Factors
D055233:Cornified Envelope Proline-Rich Proteins; D058851:GPI-Linked Proteins; D005904:Glial Fibrillary Acidic Protein; C434114:Lce3c protein, mouse; C104739:Mag protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D010742:Phospholipid Ethers; D011506:Proteins; D011956:Receptors, Cell Surface; C000603201:Rtn4 protein, mouse; C419790:Rtn4r protein, mouse; D018490:Serotonin Agents; C055096:1-O-octadecyl-2-O-methylglycerol-3-glucopyranoside; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D005947:Glucose; D003891:Desipramine