Dynamics of oligodendrocyte generation in multiple sclerosis
Open accessAbstract
Oligodendrocytes wrap nerve fibres in the central nervous system with layers of specialized cell membrane to form myelin sheaths 1. Myelin is destroyed by the immune system in multiple sclerosis, but myelin is thought to regenerate and neurological function can be recovered. In animal models of demyelinating disease, myelin is regenerated by newly generated oligodendrocytes, and remaining mature oligodendrocytes do not seem to contribute to this process 2-4. Given the major differences in the dynamics of oligodendrocyte generation and adaptive myelination between rodents and humans 5-9, it is not clear how well experimental animal models reflect the situation in multiple sclerosis. Here, by measuring the integration of 14 C derived from nuclear testing in genomic DNA 10, we assess the dynamics of oligodendrocyte generation in patients with multiple sclerosis. The generation of new oligodendrocytes was increased several-fold in normal-appearing white matter in a subset of individuals with very aggressive multiple sclerosis, but not in most subjects with the disease, demonstrating an inherent potential to substantially increase oligodendrocyte generation that fails in most patients. Oligodendrocytes in shadow plaques-thinly myelinated lesions that are thought to represent remyelinated areas-were old in patients with multiple sclerosis. The absence of new oligodendrocytes in shadow plaques suggests that remyelination of lesions occurs transiently or not at all, or that myelin is regenerated by pre-existing, and not new, oligodendrocytes in multiple sclerosis. We report unexpected oligodendrocyte generation dynamics in multiple sclerosis, and this should guide the use of current, and the development of new, therapies.
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Adult oligodendrocytes that withstand the demyelinating event may also contribute to myelin repair.
“Additionally, findings from some studies suggest that adult oligodendrocytes, which withstand the demyelinating event, may also contribute to myelin repair [101,102].”
From How to Use the Cuprizone Model to Study De- and Remyelination (2024) · cites this paper as [102]
Oligodendrocyte precursor cells in cortex and white matter differ in their propensity for terminal differentiation, and cortical oligodendrocytes reach their final number much later in life than in white matter.
“oligodendrocyte precursor cells in cortex and white matter were shown to differ in their propensity for terminal differentiation, and cortical oligodendrocytes reach their final number much later in life than in the white matter, as inferred from 14C incorporation.48”
From BCAS1-positive oligodendrocytes enable efficient cortical remyelination in multiple sclerosis (2025) · cites this paper as [48]
The paper reports 14C measurements of oligodendrocytes in white matter (Oligodendrocyte generation dynamics in multiple sclerosis, page unavailable). Searches for cortex, cortical oligodendrocyte numbers, and cortex–white-matter differentiation found no passage comparing those regions or stating when their oligodendrocytes reach their final numbers. (LLM, conf=0.76)
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- Authors
- Yeung, M. S. Y., Djelloul, M., Steiner, E., Bernard, S., Salehpour, M., Possnert, G., Brundin, L., & Frisén, J.
- Affiliations
- Karolinska Institutet (SE)
- Lyon 1 Université (FR)
- Uppsala University (SE)
- Karolinska University Hospital (SE)
- Corresponding author
- Frisén, Jonas
- ORCID
- Venue
- Nature
- Published
- 2019-01-23
- Volume
- 566
- Issue
- 7745
- Pages
- 538-542
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC6420067
- OpenAlex
- W2913848851
- Cited by
- 376
- References
- 39
- Citations by year
- 2026: 23 · 2025: 50 · 2024: 50 · 2023: 51 · 2022: 58 · 2021: 53 · 2020: 58 · 2019: 32
- FWCI
- 36.99
- Type
- journal article
- Language
- en
- Update notices
- correction (2019-02-05)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion, other-oa)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Cleveland Clinic
- Torsten Söderbergs Stiftelse
- Swedish Cancer Foundation
- Multiple Sclerosis Society (207495)
- Knut och Alice Wallenbergs Stiftelse
- Vetenskapsrådet
- Lerner Research Institute, Cleveland Clinic
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- multiple sclerosis, oligodendrocyte generation, remyelination, normal-appearing white matter, demyelinating disease, disease aggressiveness
- MeSH terms
- Remyelination, Adult, Aging, Cell Differentiation, Cell Separation, Female, Humans, Male, Multiple Sclerosis, Myelin Sheath, Oligodendroglia, Case-Control Studies, Age of Onset, Cell Proliferation, White Matter
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