Lack of interferon-beta leads to accelerated remyelination in a toxic model of central nervous system demyelination.
Interferon-beta (IFN-beta) 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-beta 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-beta 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-beta 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-beta leads to more efficient recruitment and proliferation of OPC already during demyelination, thus allowing early remyelination. These results demonstrate that IFN-beta is able to alter remyelination in the absence of an immune-mediated demyelination.
Trebst
Corinna
C
Department of Neurology, Medical School Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
Heine
Sandra
S
Lienenklaus
Stefan
S
Lindner
Maren
M
Baumgärtner
Wolfgang
W
Weiss
Siegfried
S
Stangel
Martin
M
D000818:Animals; D001253:Astrocytes / Q000276:immunology / Q000378:metabolism; D001369:Axons / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002614:Chelating Agents / Q000633:toxicity; D003471:Cuprizone / Q000633:toxicity; D004195:Disease Models, Animal; D005911:Gliosis / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D016899:Interferon-beta / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000276:immunology / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D009186:Myelin Sheath / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D020127:Recovery of Function / Q000235:genetics / Q000276:immunology
D002614:Chelating Agents; D003471:Cuprizone; D016899:Interferon-beta