Pivotal role of choline metabolites in remyelination.

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.

• Authors: Thomas Skripuletz, Arndt Manzel, Karoline Gropengießer, Nora Schäfer, Viktoria Gudi, Vikramjeet Singh, Laura Salinas Tejedor, Stefanie Jörg, Anna Hammer, Elke Voss, Franca Vulinovic, Diane Degen, Rebecca Wolf, De-Hyung Lee, Refik Pul, Darius Moharregh-Khiabani, Wolfgang Baumgärtner, Ralf Gold, Ralf A Linker, Martin Stangel
• Journal: Brain : a journal of neurology (Brain) Vol. 138 Issue Pt 2 Pg. 398-413 (Feb 2015) ISSN: 1460-2156 [Electronic] England
• PMID: 25524711 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: [email protected].

Chemical References

• Chelating Agents
• Nootropic Agents
• Cytidine Diphosphate Choline
• Cuprizone
• Choline

Topics

• Animals
• Cell Proliferation (drug effects)
• Chelating Agents
• Choline (metabolism)
• Cuprizone
• Cytidine Diphosphate Choline (pharmacology)
• Demyelinating Diseases (chemically induced, metabolism)
• Mice
• Mice, Inbred C57BL
• Myelin Sheath (drug effects)
• Neural Stem Cells (drug effects)
• Neuroglia (drug effects)
• Nootropic Agents (pharmacology)
• Oligodendroglia (drug effects)
• Rats
• Rats, Sprague-Dawley
• T-Lymphocytes (drug effects)