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The Journal of Neuroscience, January 4, 2006, 26(1):328-332; doi:10.1523/JNEUROSCI.2615-05.2006

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BRIEF COMMUNICATION
Myelin Impairs CNS Remyelination by Inhibiting Oligodendrocyte Precursor Cell Differentiation

Mark R. Kotter, Wen-Wu Li, Chao Zhao, and Robin J. M. Franklin

Cambridge Centre for Brain Repair and Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, United Kingdom

Demyelination in the adult CNS can be followed by extensive repair. However, in multiple sclerosis, the differentiation of oligodendrocyte lineage cells present in demyelinated lesions is often inhibited by unknown factors. In this study, we test whether myelin debris, a feature of demyelinated lesions and an in vitro inhibitor of oligodendrocyte precursor differentiation, affects remyelination efficiency. Focal demyelinating lesions were created in the adult rat brainstem, and the naturally generated myelin debris was augmented by the addition of purified myelin. After quantification of myelin basic protein mRNA expression from lesion material obtained by laser capture microdissection and supported by histological data, we found a significant impairment of remyelination, attributable to an arrest of the differentiation and not the recruitment of oligodendrocyte precursor cells. These data identify myelin as an inhibitor of remyelination as well as its well documented inhibition of axon regeneration.

Key words: regeneration; remyelination; oligodendrocyte precursor cell; myelin; differentiation; macrophage

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Received June 24, 2005; revised November 7, 2005; accepted November 14, 2005.

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