Retinoid X receptor gamma signaling accelerates CNS remyelination
Open accessAbstract
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.
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M1 and M2-associated genes were significantly upregulated in a microarray screen of a remyelinating lesion of the rat caudal cerebellar peduncles in vivo.
“A custom qPCR array plate (SABiosciences) was designed to include primers for M1 and M2-associated genes that were detected as being significantly upregulated in a microarray screen of a remyelinating lesion of the rat caudal cerebellar peduncles in vivo18.”
From M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination (2013) · cites this paper as [18]
The Results section, “Increased Rxrg transcripts in CNS remyelinating lesions” (page unavailable), reports a microarray screen of rat caudal cerebellar peduncle lesions and identifies significantly differentially expressed genes, including inflammation-associated genes expressed more highly at 5 days post-lesion. Our copy does not identify those genes as M1- or M2-associated or establish that the genes selected for the citing paper’s qPCR plate were significantly upregulated. (LLM, conf=0.84)
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Cites
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9-cis retinoic acid is a high affinity ligand for the retinoid X receptor
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“9- cis -retinoic acid improves CNS remyelination 9- cis -retinoic acid (9cRA), an isomer of the vitamin A-derived all- trans retinoic acid, is a known ligand for RXR activatio”
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- Authors
- Huang, J. K., Jarjour, A. A., Nait Oumesmar, B., Kerninon, C., Williams, A., Krezel, W., Kagechika, H., Bauer, J., Zhao, C., Evercooren, A. B.-V., Chambon, P., ffrench-Constant, C., & Franklin, R. J. M.
- Affiliations
- University of Cambridge (GB)
- MRC Centre for Regenerative Medicine (GB)
- Centre National de la Recherche Scientifique (FR)
- Tokyo Medical and Dental University (JP)
- Institut de génétique et de biologie moléculaire et cellulaire (FR)
- Corresponding author
- Franklin, Robin J M
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2010-12-05
- Volume
- 14
- Issue
- 1
- Pages
- 45-53
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC4013508
- OpenAlex
- W2145016172
- Cited by
- 547
- References
- 3
- Citations by year
- 2026: 31 · 2025: 32 · 2024: 33 · 2023: 25 · 2022: 37 · 2021: 44 · 2020: 31 · 2019: 45 · 2018: 34 · 2017: 40 · 2016: 31 · 2015: 41 · 2014: 25 · 2013: 42 · 2012: 27
- FWCI
- 9.38
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion, other-oa)
- HAL (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
- UEA Digital Repository (University of East Anglia) (submittedVersion)
- Funders
- Wellcome Trust (089000)
- Parkinson's UK (G0909)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Keywords
- retinoid X receptor gamma, remyelination, oligodendrocyte differentiation, oligodendrocyte precursor cells, demyelination, multiple sclerosis, gene expression profiling, 9-cis-retinoic acid, cerebellar slice cultures, central nervous system regeneration
- MeSH terms
- Alitretinoin, Retinoic Acid Receptor gamma, Aged, Animals, Benzoates, Biphenyl Compounds, Cell Differentiation, Cells, Cultured, Central Nervous System, Cerebellum, Demyelinating Diseases, Female, Humans, Male, Middle Aged, Multiple Sclerosis, Myelin Sheath, Nerve Regeneration, Neurotoxins, Oligodendroglia, Stem Cells, Tretinoin, Rats, Sprague-Dawley, Receptors, Retinoic Acid, Mice, Knockout, Cell Lineage, Gene Expression Profiling, RNA Interference, Mice, Rats
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