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.
journal_name
Nat Neuroscijournal_title
Nature neuroscienceauthors
Huang JK,Jarjour AA,Nait Oumesmar B,Kerninon C,Williams A,Krezel W,Kagechika H,Bauer J,Zhao C,Baron-Van Evercooren A,Chambon P,Ffrench-Constant C,Franklin RJMdoi
10.1038/nn.2702subject
Has Abstractpub_date
2011-01-01 00:00:00pages
45-53issue
1eissn
1097-6256issn
1546-1726journal_volume
14pub_type
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