Article Dans Une Revue Nature Neuroscience Année : 2010

Retinoid X receptor gamma signaling accelerates CNS remyelination

Résumé

The molecular basis of CNS myelin regeneration (remyelination) is poorly understood. Here we generate a comprehensive transcriptional profile of the separate stages of spontaneous remyelination following focal demyelination in the rat CNS and show transcripts encoding retinoid acid receptor RXR-gamma is highly differentially expressed during remyelination. We find that oligodendrocyte lineage cells express RXR-gamma in rat tissues undergoing remyelination and in active and remyelinated MS lesions. RXR-gamma knockdown by RNA interference or RXR-specific antagonists severely inhibit oligodendrocyte differentiation in culture. In RXR-gamma deficient mice, adult oligodendrocyte precursor cells efficiently repopulate lesions following demyelination, but display delayed differentiation into mature oligodendrocytes. Administration of the RXR agonist 9-cis-retinoic acid to demyelinated cerebellar slice cultures and to aged rats following demyelination results in more remyelinated axons. RXR-gamma is therefore a positive regulator of endogenous oligodendrocyte precursor cell differentiation and remyelination, and may be a pharmacological target for CNS regenerative therapy.

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hal-00598183 , version 1 (05-06-2011)

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Jeffrey K Huang, Andrew A Jarjour, Brahim Nait Oumesmar, Christophe Kerninon, Anna Williams, et al.. Retinoid X receptor gamma signaling accelerates CNS remyelination. Nature Neuroscience, 2010, ⟨10.1038/nn.2702⟩. ⟨hal-00598183⟩
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