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Brain. 2015 Feb;138(Pt 2):398-413. doi: 10.1093/brain/awu358. Epub 2014 Dec 17.

Pivotal role of choline metabolites in remyelination.

Author information

1
1 Department of Neurology, Hannover Medical School, 30625 Hannover, Germany.
2
2 Ruhr-University Bochum, International Graduate School of Neuroscience, 44801 Bochum, Germany 3 Department of Neurology, University Hospital Erlangen, 91054 Erlangen, Germany.
3
1 Department of Neurology, Hannover Medical School, 30625 Hannover, Germany 4 Centre for Systems Neuroscience, 30559 Hannover, Germany.
4
3 Department of Neurology, University Hospital Erlangen, 91054 Erlangen, Germany.
5
4 Centre for Systems Neuroscience, 30559 Hannover, Germany 5 Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
6
6 Department of Neurology, St Josef Hospital, Ruhr-University Bochum, 44791 Bochum, Germany.
7
1 Department of Neurology, Hannover Medical School, 30625 Hannover, Germany 4 Centre for Systems Neuroscience, 30559 Hannover, Germany Stangel.Martin@MH-Hannover.de.

Abstract

Neuroprotective approaches for central nervous system regeneration have not been successful in clinical practice so far and compounds that enhance remyelination are still not available for patients with multiple sclerosis. The objective of this study was to determine potential regenerative effects of the substance cytidine-5'-diphospho (CDP)-choline in two different murine animal models of multiple sclerosis. The effects of exogenously applied CDP-choline were tested in murine myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis. In addition, the cuprizone-induced mouse model of de- and remyelination was used to specifically test the hypothesis that CDP-choline directly increases remyelination. We found that CDP-choline ameliorated the disease course of experimental autoimmune encephalomyelitis and exerted beneficial effects on myelin, oligodendrocytes and axons. After cuprizone-induced demyelination, CDP-choline effectively enhanced myelin regeneration and reversed motor coordination deficits. The increased remyelination arose from an increase in the numbers of proliferating oligodendrocyte precursor cells and oligodendrocytes. Further in vitro studies suggest that this process is regulated by protein kinase C. We thus identified a new mechanism to enhance central nervous system remyelination via the choline pathway. Due to its regenerative action combined with an excellent safety profile, CDP-choline could become a promising substance for patients with multiple sclerosis as an add-on therapy.

KEYWORDS:

EAE; demyelination; neuroinflammation; oligodendrocyte; remyelination

PMID:
25524711
DOI:
10.1093/brain/awu358
[Indexed for MEDLINE]

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