Pivotal role of choline metabolites in remyelination

Skripuletz T, Manzel A, Gropengieer K, Schaefer N, Gudi V, Singh V, Tejedor LS, Joerg S, Hammer A, Voss E, Vulinovic F, Degen D, Wolf R, Lee DH, Pul R, Moharregh-Khiabani D, Baumgaertner W, Gold R, Linker R, Stangel M (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Brain Oxford University Press

Book Volume: 138

Pages Range: 398-413

Journal Issue: Pt 2

DOI: 10.1093/brain/awu358

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 with CRIS profile

Rebecca Wolf Medizinische Fakultät Ralf Linker Department of Neurology

Involved external institutions

Ruhr-Universität Bochum (RUB) DE Germany (DE) Stiftung Tierärztliche Hochschule Hannover (TiHo) DE Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School DE Germany (DE)

How to cite

APA:

Skripuletz, T., Manzel, A., Gropengieer, K., Schaefer, N., Gudi, V., Singh, V.,... Stangel, M. (2015). Pivotal role of choline metabolites in remyelination. Brain, 138(Pt 2), 398-413. https://dx.doi.org/10.1093/brain/awu358

MLA:

Skripuletz, Thomas, et al. "Pivotal role of choline metabolites in remyelination." Brain 138.Pt 2 (2015): 398-413.

BibTeX: Download