Neuromyelitis optica MOG-IgG causes reversible lesions in mouse brain

Acta Neuropathol Commun. 2014 Mar 31:2:35. doi: 10.1186/2051-5960-2-35.

Abstract

Introduction: Antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) are present in some neuromyelitis optica patients who lack antibodies against aquaporin-4 (AQP4-IgG). The effects of neuromyelitis optica MOG-IgG in the central nervous system have not been investigated in vivo. We microinjected MOG-IgG, obtained from patients with neuromyelitis optica, into mouse brains and compared the results with AQP4-IgG.

Results: MOG-IgG caused myelin changes and altered the expression of axonal proteins that are essential for action potential firing, but did not produce inflammation, axonal loss, neuronal or astrocyte death. These changes were independent of complement and recovered within two weeks. By contrast, AQP4-IgG produced complement-mediated myelin loss, neuronal and astrocyte death with limited recovery at two weeks.

Conclusions: These differences mirror the better outcomes for MOG-IgG compared with AQP4-IgG patients and raise the possibility that MOG-IgG contributes to pathology in some neuromyelitis optica patients.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aquaporin 4 / immunology
  • Astrocytes / drug effects
  • Brain Injuries / chemically induced*
  • Brain Injuries / immunology
  • Brain Injuries / pathology
  • Cell Adhesion Molecules, Neuronal / metabolism
  • Humans
  • Immunoglobulin G / toxicity*
  • Mice
  • Myelin Basic Protein / metabolism
  • Myelin-Oligodendrocyte Glycoprotein / immunology*
  • Nerve Tissue Proteins / metabolism
  • Neuromyelitis Optica / immunology*
  • Neuromyelitis Optica / metabolism
  • Neurons / drug effects
  • Neurons / pathology
  • Sodium Channels / metabolism
  • Time Factors

Substances

  • Aquaporin 4
  • Cell Adhesion Molecules, Neuronal
  • Cntnap1 protein, mouse
  • Immunoglobulin G
  • Myelin Basic Protein
  • Myelin-Oligodendrocyte Glycoprotein
  • Nerve Tissue Proteins
  • Sodium Channels