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Myelin Impairs CNS Remyelination by Inhibiting Oligodendrocyte Precursor Cell Differentiation
Open accessAbstract
Demyelination in the adult CNS can be followed by extensive repair. However, in multiple sclerosis, the differentiation of oligodendrocyte lineage cells present in demyelinated lesions is often inhibited by unknown factors. In this study, we test whether myelin debris, a feature of demyelinated lesions and an in vitro inhibitor of oligodendrocyte precursor differentiation, affects remyelination efficiency. Focal demyelinating lesions were created in the adult rat brainstem, and the naturally generated myelin debris was augmented by the addition of purified myelin. After quantification of myelin basic protein mRNA expression from lesion material obtained by laser capture microdissection and supported by histological data, we found a significant impairment of remyelination, attributable to an arrest of the differentiation and not the recruitment of oligodendrocyte precursor cells. These data identify myelin as an inhibitor of remyelination as well as its well documented inhibition of axon regeneration.
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In the citing paper
“they also exhibit regenerative properties through the phagocytosis of myelin debris3, 4 and secretion of growth/neurotrophic factors5.”
From M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination (2013) · cites this paper as [3]
In the citing paper
“Efficient myelin debris removal and clearance by phagocytic cells are critical to eliminate inhibitory signals interfering with OPC activation, recruitment to the site of demyelination and/or differentiation into myelinating mature OLs [14, 26, 27].”
From TREM2 activation on microglia promotes myelin debris clearance and remyelination in a model of multiple sclerosis (2020) · cites this paper as [26]
In the citing paper
“One critical role for microglia during demyelination is the clearance of myelin debris, which acts as an inhibitor of remyelination [192–194].”
From Oligodendrocyte death and myelin loss in the cuprizone model: an updated overview of the intrinsic and extrinsic causes of cuprizone demyelination (2022) · cites this paper as [194]
In the citing paper
“Long-term demyelination occurs post-SCI, with lipid-containing myelin debris being absorbed and processed by inflammatory cells, including microglia—a process crucial for paving the way for regenerative reactions and inflammation resolution [9–11].”
From miR-223 accelerates lipid droplets clearance in microglia following spinal cord injury by upregulating ABCA1 (2024) · cites this paper as [9]
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Metadata
- Authors
- Kotter, M. R., Li, W.-W., Zhao, C., & Franklin, R. J. M.
- Affiliations
- University of Cambridge (GB)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2006-01-04
- Volume
- 26
- Issue
- 1
- Pages
- 328-332
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6674302
- OpenAlex
- W2094044389
- Cited by
- 768
- References
- 30
- Citations by year
- 2026: 24 · 2025: 39 · 2024: 63 · 2023: 56 · 2022: 48 · 2021: 56 · 2020: 46 · 2019: 58 · 2018: 34 · 2017: 41 · 2016: 39 · 2015: 40 · 2014: 34 · 2013: 43 · 2012: 25
- FWCI
- 15.22
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, public-domain)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Raymond and Beverly Sackler Foundation
- Multiple Sclerosis Society
- Austrian Science Fund
- Topics
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- remyelination, myelin debris, oligodendrocyte precursor cells, oligodendrocyte differentiation, demyelination, multiple sclerosis, myelin basic protein, demyelinating lesions, axon regeneration, central nervous system repair
- MeSH terms
- Animals, Cell Differentiation, Central Nervous System, Female, Growth Inhibitors, Myelin Sheath, Nerve Fibers, Myelinated, Neural Inhibition, Oligodendroglia, Stem Cells, Rats, Sprague-Dawley, Rats
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