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Lack of interferon-beta leads to accelerated remyelination in a toxic model of central nervous system demyelination

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Abstract

Interferon-beta (IFN-β) is a pleiotropic cytokine that is known to modulate the immune response in multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system (CNS). Spontaneous remyelination and repair mechanisms in MS are mostly insufficient and contribute to clinical disability. Here, we investigated whether IFN-β has a potential in modifying the extent of de- and remyelination in a toxic model of CNS demyelination induced by the copper chelator cuprizone. IFN-β deficient (k/o) mice showed an accelerated spontaneous remyelination. However, the amount of remyelination after 6 weeks did not differ between the two groups. Demyelination in IFN-β k/o mice was paralleled by a diminished astrocytic and microglia response as compared with wildtype controls, whereas the accelerated remyelination was paralleled by an increased number of oligodendrocyte precursor cells (OPC) within the demyelinated lesion at the beginning of the remyelination phase. We hypothesize that the absence of IFN-β leads to more efficient recruitment and proliferation of OPC already during demyelination, thus allowing early remyelination. These results demonstrate that IFN-β is able to alter remyelination in the absence of an immune-mediated demyelination.

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Acknowledgments

The work was partially supported by the Deutsche Forschungsgemeinschaft (DFG, SFB 566, project A11).

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Authors and Affiliations

  1. Department of Neurology, Medical School Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Germany

    Corinna Trebst, Sandra Heine, Maren Lindner & Martin Stangel

  2. Center for Systems Neuroscience, Hannover, Germany

    Maren Lindner, Wolfgang Baumgärtner & Martin Stangel

  3. Molecular Immunology Group, Helmholtz Center for Infection Research, Braunschweig, Germany

    Stefan Lienenklaus & Siegfried Weiss

  4. Department of Pathology, Veterinary School Hannover, Hannover, Germany

    Wolfgang Baumgärtner

Authors
  1. Corinna Trebst
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  2. Sandra Heine
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  3. Stefan Lienenklaus
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  4. Maren Lindner
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  5. Wolfgang Baumgärtner
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  6. Siegfried Weiss
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  7. Martin Stangel
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Corresponding author

Correspondence to Martin Stangel.

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The first two authors contributed equally to this work.

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Trebst, C., Heine, S., Lienenklaus, S. et al. Lack of interferon-beta leads to accelerated remyelination in a toxic model of central nervous system demyelination. Acta Neuropathol 114, 587–596 (2007). https://doi.org/10.1007/s00401-007-0300-z

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  • DOI: https://doi.org/10.1007/s00401-007-0300-z

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