Blockade of Nogo-66, myelin-associated glycoprotein, and oligodendrocyte myelin glycoprotein by soluble Nogo-66 receptor promotes axonal sprouting and recovery after spinal injury

J Neurosci. 2004 Nov 17;24(46):10511-20. doi: 10.1523/JNEUROSCI.2828-04.2004.

Abstract

The growth of injured axons in the adult mammalian CNS is limited after injury. Three myelin proteins, Nogo, MAG (myelin-associated glycoprotein), and OMgp (oligodendrocyte myelin glycoprotein), bind to the Nogo-66 receptor (NgR) and inhibit axonal growth in vitro. Transgenic or viral blockade of NgR function allows axonal sprouting in vivo. Here, we administered the soluble function-blocking NgR ectodomain [aa 27-310; NgR(310)ecto] to spinal-injured rats. Purified NgR(310)ecto-Fc protein was delivered intrathecally after midthoracic dorsal over-hemisection. Axonal sprouting of corticospinal and raphespinal fibers in NgR(310)ecto-Fc-treated animals correlates with improved spinal cord electrical conduction and improved locomotion. The ability of soluble NgR(310)ecto to promote axon growth and locomotor recovery demonstrates a therapeutic potential for NgR antagonism in traumatic spinal cord injury.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Axons / metabolism
  • Axons / physiology*
  • Evoked Potentials, Motor
  • Female
  • GPI-Linked Proteins
  • Injections, Spinal
  • Motor Activity
  • Myelin Proteins / antagonists & inhibitors*
  • Myelin-Associated Glycoprotein / antagonists & inhibitors*
  • Myelin-Associated Glycoprotein / metabolism*
  • Myelin-Oligodendrocyte Glycoprotein
  • Nogo Proteins
  • Nogo Receptor 1
  • Oligodendroglia / metabolism
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cell Surface
  • Receptors, Peptide / physiology*
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / pharmacology
  • Serotonin / metabolism
  • Solubility
  • Spinal Cord / physiopathology
  • Spinal Cord / ultrastructure
  • Spinal Cord Injuries / metabolism
  • Spinal Cord Injuries / pathology*
  • Spinal Cord Injuries / physiopathology

Substances

  • GPI-Linked Proteins
  • Mog protein, rat
  • Myelin Proteins
  • Myelin-Associated Glycoprotein
  • Myelin-Oligodendrocyte Glycoprotein
  • NgR(310) Ecto-Fc protein
  • Nogo Proteins
  • Nogo Receptor 1
  • Omg protein, rat
  • Peptide Fragments
  • Receptors, Cell Surface
  • Receptors, Peptide
  • Recombinant Fusion Proteins
  • Rtn4 protein, rat
  • Rtn4r protein, rat
  • Serotonin