Repository logo
 

Oligodendrocyte death and myelin loss in the cuprizone model: an updated overview of the intrinsic and extrinsic causes of cuprizone demyelination.

Published version
Peer-reviewed

Change log

Authors

Zirngibl, Martin 
Assinck, Peggy 
Sizov, Anastasia 
Caprariello, Andrew V 
Plemel, Jason R 

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.

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

Keywords

Astrocytes, CNS, Cell death, Cuprizone, Demyelination, Inflammation, Microglia, Multiple Sclerosis, Oligodendrocytes, Animals, Astrocytes, Cuprizone, Demyelinating Diseases, Disease Models, Animal, Mice, Mice, Inbred C57BL, Microglia, Myelin Sheath, Oligodendroglia

Journal Title

Mol Neurodegener

Conference Name

Journal ISSN

1750-1326
1750-1326

Volume Title

17

Publisher

Springer Science and Business Media LLC