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Cited by 172Multiple Sclerosis Research StudiesNeurogenesis and neuroplasticity mechanismsNerve injury and regeneration

Episodic demyelination and subsequent remyelination within the murine central nervous system: changes in axonal calibre

Mason, J. L., Langaman, C., Morell, P., Suzuki, K., Matsushima, G. K.·2001·Neuropathology and Applied Neurobiology
DOI 10.1046/j.0305-1846.2001.00301.x
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Abstract

Exposure of young adult C57BL/6 mice to cuprizone in the diet initiated profound and synchronous demyelination of the corpus callosum, which was virtually complete by 4 weeks of exposure. Interestingly, even in the face of a continued exposure to cuprizone, there was spontaneous remyelination 2 weeks later. This remyelination preferentially involved smaller calibre axons. There was a suggestion of yet another cycle of demyelination (at 10 weeks) and remyelination (at 12 weeks), but by 16 weeks of exposure, the regenerative capacity was exhausted and the animals were near death. The relapsing–remitting pattern suggests this may be a useful model for certain human demyelinating disorders. In contrast to the above chronic model, the corpus callosum from mice exposed to cuprizone for only 6 weeks continued to remyelinate, with 67% of the axons being myelinated or remyelinated at 10 weeks. Interestingly, a significant reduction in the mean value for axonal diameter was observed during acute demyelination. Upon remyelination, however, the axonal calibre distribution returned to near‐normal. In contrast, when mice were maintained on a cuprizone diet for 16 weeks, the mean value for axonal diameter was reduced to 60% of normal. These results provide further evidence that the interactions between oligodendrocytes and axons alter axonal calibre.

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Crossref · 10.1046/j.0305-1846.2001.00301.x

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  • Continuous exposure of C57BL/6 mice to cuprizone results in two cycles of demyelination and remyelination, followed by chronic demyelination from which animals do not recover.

    “In contrast, the continuous exposure of C57BL/6 mice to cuprizone results in a pattern of two cycles of demyelination and remyelination, followed by chronic demyelination from which animals do not recover 36, 39.”

    From SJL Mice Exposed to Cuprizone Intoxication Reveal Strain and Gender Pattern Differences in Demyelination (2009) · cites this paper as [36]

  • Unlike male C57BL/6 mice, which show three cycles of demyelination over 13 weeks, SJL mice appear to demyelinate gradually once during these time points, and the demyelination is incomplete.

    “Thus, unlike male C57BL/6 mice, which show three cycles of demyelination while on continuous exposure to cuprizone over 13 weeks (36), SJL mice appear to demyelinate gradually once during these time points; however, the demyelination is incomplete.”

    From SJL Mice Exposed to Cuprizone Intoxication Reveal Strain and Gender Pattern Differences in Demyelination (2009) · cites this paper as [36]

  • Previous studies have shown that LFB-PAS scores are reflective of trends in demyelination when compared with percent myelinated fibers counted in electron micrographs.

    “Previous studies have shown that LFB–PAS scores are reflective to the trends in demyelination when compared with percent myelinated fibers that are counted in electron micrographs 29, 36.”

    From SJL Mice Exposed to Cuprizone Intoxication Reveal Strain and Gender Pattern Differences in Demyelination (2009) · cites this paper as [36]

  • C57BL/6 mice experience a spontaneous partial remyelination after 6 weeks and then continue to demyelinate further when exposed continuously to cuprizone.

    “In addition, C57BL/6 mice experience a spontaneous partial remyelination after 6 weeks and then continue to demyelinate further when exposed continuously to cuprizone 36, 39.”

    From SJL Mice Exposed to Cuprizone Intoxication Reveal Strain and Gender Pattern Differences in Demyelination (2009) · cites this paper as [36]

  • Long-term feeding of cuprizone induces an episodic sequence of demyelinating and remyelinating events, which becomes ineffective over time, progressing to a chronic state of demyelination.

    “Indeed, long-term feeding of cuprizone induces an episodic sequence of demyelinating and remyelinating events, which becomes ineffective over time, progressing to a chronic state of demyelination [26].”

    From How to Use the Cuprizone Model to Study De- and Remyelination (2024) · cites this paper as [26]

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Authors
Mason, J. L., Langaman, C., Morell, P., Suzuki, K., & Matsushima, G. K.
Affiliations
University of North Carolina at Chapel Hill (US)
Corresponding author
Matsushima, G. K.
ORCID
Suzuki, K.
Venue
Neuropathology and Applied Neurobiology
Publisher
Wiley
Published
2001-02
Volume
27
Issue
1
Pages
50-58
ISSN
  • 0305-1846 (ISSN-L)
  • 1365-2990
DOI
10.1046/j.0305-1846.2001.00301.x
OpenAlex
W2156549416
Cited by
172
References
27
Citations by year
2026: 3 · 2025: 3 · 2024: 6 · 2023: 5 · 2022: 4 · 2021: 3 · 2020: 6 · 2019: 13 · 2018: 6 · 2017: 8 · 2016: 13 · 2015: 12 · 2014: 9 · 2013: 6 · 2012: 4
FWCI
3.32
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 323 d)
Locations
  • Neuropathology and Applied Neurobiology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Multiple Sclerosis Society
  • National Institutes of Health (RG2754A1, 5r01ns011615-29, 5r01ns037815-05, 5r29ns035372-05)
  • National Institute of Neurological Disorders and Stroke (NS 24453, NS37815, R01NS024453, NS-11615, NS-35372)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
Keywords
cuprizone, demyelination, remyelination, axon diameter, corpus callosum, demyelinating disease, C57BL/6 mice
MeSH terms
Amidines, Animals, Axons, Central Nervous System, Chronic Disease, Corpus Callosum, Cuprizone, Demyelinating Diseases, Disease Models, Animal, Fluorescent Dyes, Mice, Inbred C57BL, Microscopy, Electron, Nerve Fibers, Myelinated, Recurrence, Remission, Spontaneous, Cell Size, Mice

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