Fingolimod does not enhance cerebellar remyelination in the cuprizone model

Maria Nordheim Alme; Agnes E Nystad; Lars Bø; Kjell-Morten Myhr; Christian A Vedeler; Stig Wergeland; Øivind Torkildsen

doi:10.1016/j.jneuroim.2015.06.006

Fingolimod does not enhance cerebellar remyelination in the cuprizone model

J Neuroimmunol. 2015 Aug 15:285:180-6. doi: 10.1016/j.jneuroim.2015.06.006. Epub 2015 Jun 19.

Authors

Maria Nordheim Alme¹, Agnes E Nystad², Lars Bø³, Kjell-Morten Myhr⁴, Christian A Vedeler⁵, Stig Wergeland⁶, Øivind Torkildsen⁷

Affiliations

¹ Department of Clinical Medicine, University of Bergen, Pb 7804, 5020 Bergen, Norway. Electronic address: [email protected].
² Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital, Haukelandsveien 22, 5021 Bergen, Norway; Kristian Gerhard Jebsen MS Research Centre, Department of Clinical Medicine, University of Bergen, Pb 7804, 5020 Bergen, Norway. Electronic address: [email protected].
³ Department of Clinical Medicine, University of Bergen, Pb 7804, 5020 Bergen, Norway; Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital, Haukelandsveien 22, 5021 Bergen, Norway; Kristian Gerhard Jebsen MS Research Centre, Department of Clinical Medicine, University of Bergen, Pb 7804, 5020 Bergen, Norway. Electronic address: [email protected].
⁴ Department of Clinical Medicine, University of Bergen, Pb 7804, 5020 Bergen, Norway; Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital, Haukelandsveien 22, 5021 Bergen, Norway; Kristian Gerhard Jebsen MS Research Centre, Department of Clinical Medicine, University of Bergen, Pb 7804, 5020 Bergen, Norway. Electronic address: [email protected].
⁵ Department of Clinical Medicine, University of Bergen, Pb 7804, 5020 Bergen, Norway; Kristian Gerhard Jebsen MS Research Centre, Department of Clinical Medicine, University of Bergen, Pb 7804, 5020 Bergen, Norway; Department of Neurology, Haukeland University Hospital, Haukelandsveien 22, 5021 Bergen, Norway. Electronic address: [email protected].
⁶ Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital, Haukelandsveien 22, 5021 Bergen, Norway; Kristian Gerhard Jebsen MS Research Centre, Department of Clinical Medicine, University of Bergen, Pb 7804, 5020 Bergen, Norway. Electronic address: [email protected].
⁷ Department of Clinical Medicine, University of Bergen, Pb 7804, 5020 Bergen, Norway; Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital, Haukelandsveien 22, 5021 Bergen, Norway; Kristian Gerhard Jebsen MS Research Centre, Department of Clinical Medicine, University of Bergen, Pb 7804, 5020 Bergen, Norway. Electronic address: [email protected].

PMID: 26198937
DOI: 10.1016/j.jneuroim.2015.06.006

Abstract

Fingolimod (FTY720) is approved for treatment of relapsing-remitting multiple sclerosis. In vitro studies have found that fingolimod stimulates remyelination in cerebellar slices, but in vivo animal studies have not detected any positive effect on cerebral remyelination. The discrepant findings could be a result of different mechanisms underlying cerebral and cerebellar remyelination. The cuprizone model for de- and remyelination was used to evaluate whether fingolimod had an impact on cerebellar remyelination in vivo. We found that fingolimod did not have any effect on cerebellar remyelination, number of mature oligodendrocytes, microglia or astrocytes when fed after cuprizone exposure.

Keywords: Cerebellum; Cuprizone; Demyelination; FTY720; Fingolimod; Remyelination.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cerebellum / drug effects*
Cerebellum / immunology
Cerebellum / pathology
Cuprizone / toxicity*
Demyelinating Diseases / chemically induced
Demyelinating Diseases / drug therapy*
Demyelinating Diseases / immunology
Disease Models, Animal*
Female
Fingolimod Hydrochloride
Immunosuppressive Agents / therapeutic use*
Mice
Mice, Inbred C57BL
Propylene Glycols / therapeutic use*
Sphingosine / analogs & derivatives*
Sphingosine / therapeutic use

Substances

Immunosuppressive Agents
Propylene Glycols
Cuprizone
Fingolimod Hydrochloride
Sphingosine