Promotion of central nervous system remyelination by induced differentiation of oligodendrocyte precursor cells
Objective Repair of demyelinated axons in diseases such as multiple sclerosis requires activation of the myelination program in existing or newly recruited oligodendrocyte precursor cells (OPCs). The control of OPC differentiation and initiation of myelination during repair is poorly understood. In...
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Published in | Annals of neurology Vol. 65; no. 3; pp. 304 - 315 |
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Main Authors | , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Hoboken
Wiley Subscription Services, Inc., A Wiley Company
01.03.2009
Wiley-Liss |
Subjects | |
Online Access | Get full text |
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Summary: | Objective
Repair of demyelinated axons in diseases such as multiple sclerosis requires activation of the myelination program in existing or newly recruited oligodendrocyte precursor cells (OPCs). The control of OPC differentiation and initiation of myelination during repair is poorly understood. In this study, we test the ability of anti–LINGO‐1 reagents to promote myelination in vitro and remyelination in the rodent adult central nervous system in vivo.
Methods
The effects of LINGO‐1 antagonists on the differentiation of OPCs and the promotion of myelination has been assayed using a combination of coculture and slice culture preparations. Using three different animal models of demyelination and remyelination, we morphologically and functionally assessed the effects of LINGO‐1 antagonists on OPC differentiation and myelin repair.
Results
The data indicate that in vitro treatment with antagonists of LINGO‐1 promote OPC differentiation and myelination, whereas in vivo remyelination is accelerated in lysophosphatidylcholine‐ or cuprizone‐induced demyelination. This remyelination is associated with enhanced OPC differentiation and functional recovery of conduction velocities in demyelinated axons.
Interpretation
Our studies demonstrate that LINGO‐1 antagonism promotes OPC differentiation and remyelination, and suggest LINGO‐1 functions as an inhibitor of OPC differentiation to retard central nervous system remyelination. Ann Neurol 2009;65:304–315 |
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Bibliography: | istex:012FA1ED150C3900C678CD6B1BE858BFD9C6E7A9 ArticleID:ANA21581 ark:/67375/WNG-2K61MBHG-8 Potential conflict of interest: Nothing to report. S.M. and R.H.M. contributed equally to this work. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0364-5134 1531-8249 |
DOI: | 10.1002/ana.21581 |