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Quantifying the early stages of remyelination following cuprizone-induced demyelination
Open accessAbstract
The demyelinating toxin cuprizone is used increasingly in mouse studies of central nervous system remyelination. The value of this model for such studies depends on an accurate description of its quantifiable features. We therefore investigated histology and ultrastructure during the early oligodendrocyte differentiation phase of remyelination in mice given cuprizone and allowed to recover for 2 weeks. Limiting the dose of cuprizone to 0.2% overcame significant mouse morbidity and weight loss seen with a 0.4% dose, but the distribution of cuprizone-induced demyelination was anatomically variable. The caudal corpus callosum and dorsal hippocampal commissure mostly demyelinated at this dose, but the rostral corpus callosum and rostral cerebellar peduncles did not. This variable response, together with small axon diameters and hence thin myelin sheaths, hindered analysis of the progress of early remyelination. The proportion of myelinated and unmyelinated axons in defined regions followed expected trends, but there was pronounced variation between animals. Furthermore, group mean G ratios did not change as expected during the early stages of remyelination, and regression analysis revealed a complex relationship between axon diameter and myelin sheath thickness during this period. We also noted axonal pathology that persisted for at least 2 weeks after cuprizone withdrawal.
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Myelin formed during repair of experimental demyelination or during demyelinating injury or disease is thinner on average (larger g-ratio) than myelin formed during normal development, although this is less pronounced for smaller-diameter axons such as those in the optic nerve.
“It is well documented that myelin formed during repair of experimental demyelination or during demyelinating injury or disease is thinner on average (larger g-ratio) than myelin that is formed during normal development (e.g., Lasiene et al., 2008), although this is less pronounced for smaller-diameter axons such as those in the optic nerve (Stidworthy et al., 2003).”
From Oligodendrocyte Dynamics in the Healthy Adult CNS: Evidence for Myelin Remodeling (2013) · cites this paper as Stidworthy et al., 2003
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Metadata
- Authors
- Stidworthy, M. F., Genoud, S., Suter, U., Mantei, N., & Franklin, R. J. M.
- Affiliations
- University of Cambridge (GB)
- ETH Zurich (CH)
- Corresponding author
- Franklin, Robin J. M.
- Venue
- Brain Pathology
- Publisher
- Wiley
- Published
- 2003-07
- Volume
- 13
- Issue
- 3
- Pages
- 329-339
- ISSN
- 1015-6305 (ISSN-L)
- 1750-3639
- PMC
- PMC8095752
- OpenAlex
- W2147554232
- Cited by
- 224
- References
- 28
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 11 · 2023: 6 · 2022: 10 · 2021: 8 · 2020: 9 · 2019: 15 · 2018: 17 · 2017: 22 · 2016: 8 · 2015: 13 · 2014: 10 · 2013: 18 · 2012: 8
- FWCI
- 1.53
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Brain Pathology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- 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
- cuprizone, remyelination, demyelination, oligodendrocyte differentiation, corpus callosum, hippocampal commissure, cerebellar peduncles, axon diameter, myelin thickness, g-ratio, axonal pathology, dose-dependent toxicity, mouse model
- MeSH terms
- Animals, Axons, Chelating Agents, Corpus Callosum, Cuprizone, Demyelinating Diseases, Disease Models, Animal, Hippocampus, Mice, Inbred C57BL, Microscopy, Electron, Myelin Sheath, Regression Analysis, Sex Characteristics, Time Factors, Prosencephalon, Mice, Knockout, Mice
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