Oligodendrocyte death and myelin loss in the cuprizone model: an updated overview of the intrinsic and extrinsic causes of cuprizone demyelination.
Authors
Zirngibl, Martin
Assinck, Peggy
Sizov, Anastasia
Caprariello, Andrew V
Plemel, Jason R
Publication Date
2022-05-07Journal Title
Mol Neurodegener
ISSN
1750-1326
Publisher
Springer Science and Business Media LLC
Volume
17
Issue
1
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Zirngibl, M., Assinck, P., Sizov, A., Caprariello, A. V., & Plemel, J. R. (2022). Oligodendrocyte death and myelin loss in the cuprizone model: an updated overview of the intrinsic and extrinsic causes of cuprizone demyelination.. Mol Neurodegener, 17 (1) https://doi.org/10.1186/s13024-022-00538-8
Description
Funder: Canadian Institutes for Health Research (CA)
Funder: Natural Sciences and Engineering Research Council of Canada; doi: http://dx.doi.org/10.13039/501100000038
Funder: Fondation Brain Canada; doi: http://dx.doi.org/10.13039/100009408
Funder: Azrieli Foundation; doi: http://dx.doi.org/10.13039/501100005155
Abstract
The dietary consumption of cuprizone - a copper chelator - has long been known to induce demyelination of specific brain structures and is widely used as model of multiple sclerosis. Despite the extensive use of cuprizone, the mechanism by which it induces demyelination are still unknown. With this review we provide an updated understanding of this model, by showcasing two distinct yet overlapping modes of action for cuprizone-induced demyelination; 1) damage originating from within the oligodendrocyte, caused by mitochondrial dysfunction or reduced myelin protein synthesis. We term this mode of action 'intrinsic cell damage'. And 2) damage to the oligodendrocyte exerted by inflammatory molecules, brain resident cells, such as oligodendrocytes, astrocytes, and microglia or peripheral immune cells - neutrophils or T-cells. We term this mode of action 'extrinsic cellular damage'. Lastly, we summarize recent developments in research on different forms of cell death induced by cuprizone, which could add valuable insights into the mechanisms of cuprizone toxicity. With this review we hope to provide a modern understanding of cuprizone-induced demyelination to understand the causes behind the demyelination in MS.
Keywords
Review, Cuprizone, Multiple Sclerosis, Demyelination, Oligodendrocytes, Inflammation, Cell death, Astrocytes, Microglia, CNS
Identifiers
s13024-022-00538-8, 538
External DOI: https://doi.org/10.1186/s13024-022-00538-8
This record's URL: https://www.repository.cam.ac.uk/handle/1810/336920
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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