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Nature. 2019 Feb;566(7745):538-542. doi: 10.1038/s41586-018-0842-3. Epub 2019 Jan 23.

Dynamics of oligodendrocyte generation in multiple sclerosis.

Author information

1
Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
2
Institut Camille Jordan, CNRS UMR 5208, University of Lyon, Villeurbanne, France.
3
Department of Physics and Astronomy, Ion Physics, Uppsala University, Uppsala, Sweden.
4
Department of Clinical Neuroscience, Division of Neurology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
5
Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden. jonas.frisen@ki.se.

Abstract

Oligodendrocytes wrap nerve fibres in the central nervous system with layers of specialized cell membrane to form myelin sheaths1. 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 process2-4. Given the major differences in the dynamics of oligodendrocyte generation and adaptive myelination between rodents and humans5-9, it is not clear how well experimental animal models reflect the situation in multiple sclerosis. Here, by measuring the integration of 14C derived from nuclear testing in genomic DNA10, 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.

PMID:
30675058
PMCID:
PMC6420067
[Available on 2019-07-23]
DOI:
10.1038/s41586-018-0842-3

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