Type I interferon receptor signalling is induced during demyelination while its function for myelin damage and repair is redundant

Exp Neurol. 2009 Apr;216(2):306-11. doi: 10.1016/j.expneurol.2008.12.002. Epub 2008 Dec 14.


The type I interferons, interferon-beta and alpha (IFN-beta, IFN-alpha), are widely used for the treatment of autoimmune demyelination in the central nervous system (CNS). Their effects on de- and remyelination through the broadly expressed type I IFN receptor (IFNAR), however, are highly speculative. In order to elucidate the role of endogenous type I interferons for myelin damage and recovery we induced toxic demyelination in the absence of IFNAR1. We demonstrate that IFNAR signalling was induced during acute demyelination since the cytokine IFN-beta as well as the IFN-dependent genes IRF7, ISG15 and UBP43 were strongly upregulated. Myelin damage, astrocytic and microglia response, however, were not significantly reduced in the absence of IFNAR1. Furthermore, motor skills of IFNAR1-deficient animals during non-immune demyelination were unaltered. Finally, myelin recovery was found to be independent from endogenous IFNAR signalling, indicating a redundant role of this receptor for non-inflammatory myelin damage and repair.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Central Nervous System / metabolism
  • Central Nervous System / pathology
  • Central Nervous System / ultrastructure
  • Cuprizone / toxicity
  • Demyelinating Diseases / chemically induced
  • Demyelinating Diseases / metabolism*
  • Demyelinating Diseases / pathology
  • Demyelinating Diseases / physiopathology*
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics
  • Glial Fibrillary Acidic Protein / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Motor Activity / drug effects
  • Motor Activity / genetics
  • Motor Skills / physiology
  • Myelin Sheath / metabolism*
  • Myelin Sheath / pathology
  • Receptor, Interferon alpha-beta / deficiency
  • Receptor, Interferon alpha-beta / genetics
  • Receptor, Interferon alpha-beta / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Specific Pathogen-Free Organisms


  • Glial Fibrillary Acidic Protein
  • Receptor, Interferon alpha-beta
  • Cuprizone