Interferon-γ protects against cuprizone-induced demyelination

Xiang Gao*, Taressa A. Gillig, Ping Ye, A. Joseph D'Ercole, Glenn K. Matsushima, Brian Popko

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

Abstract

Evidence suggests that interferon-γ (IFN-γ), a proinflammatory cytokine secreted by activated T lymphocytes, contributes a deleterious effect to immune-mediated demyelinating disorders such as multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). Nevertheless, mouse strains that are normalmy resistant to EAE induction become susceptible when the gene encoding either IFN-γ or its receptor is mutated, demonstrating that the role that this cytokine plays in demyelinating disorders is complex. We have examined the effect of IFN-γ in a chemically induced model of CNS demyelination. Mice that receive through their diet the copper chelator cuprizone display extensive demyelination of the corpus cellosum. Remarkably, transgenic mice that ectopically express low levels of IFN-γ in the CNS did not display evidence of demyelination when treated with cuprizone, nor did they shows signs of oligodendroglal death, astrogliosis, or microgliosis, which are typically seen in treated animals. Myelin protein gene expression was, however, dramatically reduced in both the treated control and the transgenic animals, indicating that demyelination is not an obligatory consequence of a large diminution of myelin protein synthesis. Interestingly, the CNS of the IFN-γ-expressing mice contained elevated levels of insulin-like growth factor I, which has been demonstrated to have a protective effect against the demyelinating action of cuprizone.

Original languageEnglish (US)
Pages (from-to)338-349
Number of pages12
JournalMolecular and Cellular Neurosciences
Volume16
Issue number4
DOIs
StatePublished - Jan 1 2000

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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