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PMID: 15504325 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Nogo-66 receptor prevents raphespinal and rubrospinal axon regeneration and limits functional recovery from spinal cord injury.

Neuron ·Vol. 44 ·No. 3 ·2004-10-28 ·Pages 439-51

Kim JE, Liu BP, Park JH, Strittmatter SM

Abstract

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.

MeSH Terms

5,7-Dihydroxytryptamine/pharmacology Animals Axons/physiology Behavior, Animal Blotting, Northern/methods Blotting, Southern/methods Brain/pathology Cell Count/methods Cells, Cultured Cloning, Molecular/methods Cornified Envelope Proline-Rich Proteins Desipramine/pharmacology Disease Models, Animal Evoked Potentials, Motor/physiology Female GPI-Linked Proteins Ganglia, Spinal/cytology Glial Fibrillary Acidic Protein/metabolism Glucose/analogs & derivatives,pharmacology Growth Cones/drug effects,physiology Immunohistochemistry/methods Mice Mice, Inbred C57BL Mice, Knockout Motor Activity/physiology Myelin Proteins/genetics,metabolism,pharmacology,physiology Myelin Sheath/metabolism Myelin-Associated Glycoprotein Nerve Regeneration Neurons/cytology,drug effects Nogo Proteins Nogo Receptor 1 Phospholipid Ethers/pharmacology Proteins/metabolism Pyramidal Tracts/physiopathology Receptors, Cell Surface/genetics,metabolism,physiology Recovery of Function/physiology Serotonin/metabolism Serotonin Agents/pharmacology Spinal Cord/metabolism,physiopathology Spinal Cord Injuries/genetics,physiopathology,prevention & control Time Factors

Chemicals

Cornified Envelope Proline-Rich Proteins GPI-Linked Proteins Glial Fibrillary Acidic Protein Lce3c protein, mouse Mag protein, mouse Myelin Proteins Myelin-Associated Glycoprotein Nogo Proteins Nogo Receptor 1 Phospholipid Ethers Proteins Receptors, Cell Surface Rtn4 protein, mouse Rtn4r protein, mouse Serotonin Agents 1-O-octadecyl-2-O-methylglycerol-3-glucopyranoside 5,7-Dihydroxytryptamine Serotonin Glucose Desipramine

Authors & Affiliations

4 authors, click to expand affiliations / ORCID

Kim Ji-Eun

Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA.

Liu Betty P

Park James H

Strittmatter Stephen M

Article Info

Journal

Neuron

Abbr.

Neuron

ISSN

0896-6273

DOI

10.1016/j.neuron.2004.10.015

Published

2004-10-28

Pages

439-51

Language

English

Region

United States

NLM ID

8809320

Subset

External Links

PubMed source DOI: 10.1016/j.neuron.2004.10.015 View journal details

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Nogo-66 receptor prevents raphespinal and rubrospinal axon regeneration and limits functional recovery from spinal cord injury.

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