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Retinoid X receptor gamma signaling accelerates CNS remyelination.

TitleRetinoid X receptor gamma signaling accelerates CNS remyelination.
Publication TypeJournal Article
Year of Publication2011
AuthorsHuang JK, Jarjour AA, Oumesmar BNait, Kerninon C, Williams AC, Krezel W, Kagechika H, Bauer J, Zhao C, Van Evercooren ABaron-, Chambon P, ffrench-Constant C, Franklin RJM
JournalNat Neurosci
Date Published2011 Jan
KeywordsAged, Animals, Benzoates, Biphenyl Compounds, Cell Differentiation, Cell Lineage, Cells, Cultured, Central Nervous System, Cerebellum, Demyelinating Diseases, Female, Gene Expression Profiling, Humans, Male, Mice, Mice, Knockout, Middle Aged, Multiple Sclerosis, Myelin Sheath, Nerve Regeneration, Neurotoxins, Oligodendroglia, Rats, Rats, Sprague-Dawley, Receptors, Retinoic Acid, RNA Interference, Stem Cells, Tretinoin

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.

Alternate JournalNat. Neurosci.
PubMed ID21131950
PubMed Central IDPMC4013508
Grant List089000 / / Wellcome Trust / United Kingdom
G0701476 / / Medical Research Council / United Kingdom
/ / Wellcome Trust / United Kingdom