Myelin impairs CNS remyelination by inhibiting oligodendrocyte precursor cell differentiation.
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.
Kotter
Mark R
MR
Cambridge Centre for Brain Repair, Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, United Kingdom.
Li
Wen-Wu
WW
Zhao
Chao
C
Franklin
Robin J M
RJ
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002490:Central Nervous System / Q000502:physiology / Q000648:ultrastructure; D005260:Female; D006131:Growth Inhibitors / Q000502:physiology*; D009186:Myelin Sheath / Q000502:physiology* / Q000648:ultrastructure*; D009413:Nerve Fibers, Myelinated / Q000502:physiology / Q000648:ultrastructure*; D009433:Neural Inhibition / Q000502:physiology; D009836:Oligodendroglia / Q000502:physiology / Q000648:ultrastructure*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000502:physiology / Q000648:ultrastructure*
D006131:Growth Inhibitors