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- Title
Retinoid X receptor gamma signaling accelerates CNS remyelination.
- Authors
Huang, Jeffrey K; Jarjour, Andrew A; Nait Oumesmar, Brahim; Kerninon, Christophe; Williams, Anna; Krezel, Wojciech; Kagechika, Hiroyuki; Bauer, Julien; Zhao, Chao; Baron-Van Evercooren, Anne; Chambon, Pierre; Ffrench-Constant, Charles; Franklin, Robin J M
- Abstract
The molecular basis of CNS myelin regeneration (remyelination) is poorly understood. We generated a comprehensive transcriptional profile of the separate stages of spontaneous remyelination that follow focal demyelination in the rat CNS and found that transcripts that encode the retinoid acid receptor RXR-γ were differentially expressed during remyelination. Cells of the oligodendrocyte lineage expressed RXR-γ in rat tissues that were undergoing remyelination and in active and remyelinated multiple sclerosis lesions. Knockdown of RXR-γ by RNA interference or RXR-specific antagonists severely inhibited oligodendrocyte differentiation in culture. In mice that lacked RXR-γ, adult oligodendrocyte precursor cells efficiently repopulated lesions after demyelination, but showed delayed differentiation into mature oligodendrocytes. Administration of the RXR agonist 9-cis-retinoic acid to demyelinated cerebellar slice cultures and to aged rats after demyelination caused an increase in remyelinated axons. Our results indicate that RXR-γ is a positive regulator of endogenous oligodendrocyte precursor cell differentiation and remyelination and might be a pharmacological target for regenerative therapy in the CNS.
- Publication
Nature neuroscience, 2011, Vol 14, Issue 1, p45
- ISSN
1546-1726
- Publication type
Journal Article
- DOI
10.1038/nn.2702