Sequential myelin protein expression during remyelination reveals fast and efficient repair after central nervous system demyelination
Abstract
To understand the mechanisms of remyelination and the reasons for regeneration failure is one of the major challenges in multiple sclerosis research. This requires a good knowledge and reliable analysis of experimental models. This work was undertaken to characterize the pattern of myelin protein expression during experimental remyelination. Acute demyelination of the corpus callosum was induced by feeding of 0.3% cuprizone for 6 weeks, followed by a 10‐week remyelination period. We used a combination of Luxol fast blue (LFB) myelin staining, electron microscopy (EM) and immunohistochemistry for the myelin proteins 2′,3′‐cyclic nucleotide 3′ phosphodiesterase (CNPase), myelin basic protein (MBP), proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG). Early remyelination was detected by the re‐expression of CNPase, MBP and PLP as early as 4 days. MOG, as a marker for late differentiation of oligodendrocytes, was not detectable until 2 weeks of remyelination. EM data correlated well with the LFB myelin staining and myelin protein expression, with 50% of the axons being rapidly remyelinated within 2 weeks. While particularly MBP but also PLP and CNPase are re‐expressed very early before significant remyelination is observed by EM, the late marker MOG shows a lag behind the remyelination detected by EM. The presented data indicate that immunohistochemistry for various myelin proteins expressed early and late during myelin formation is a suitable and reliable method to follow remyelination in the cuprizone model. Furthermore, investigation of early remyelination confirms that the intrinsic repair programme is very fast and switched on within days.
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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 [29]
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- Authors
- Lindner, M., Heine, S., Haastert, K., Garde, N., Fokuhl, J., Linsmeier, F., Grothe, C., Baumgärtner, W., & Stangel, M.
- Affiliations
- Medizinische Hochschule Hannover (DE)
- Pediatrics and Genetics (US)
- University of Veterinary Medicine Hannover, Foundation (DE)
- Corresponding author
- Stangel, M.
- Venue
- Neuropathology and Applied Neurobiology
- Publisher
- Wiley
- Published
- 2007-10-26
- Volume
- 34
- Issue
- 1
- Pages
- 105-114
- ISSN
- 0305-1846 (ISSN-L)
- 1365-2990
- OpenAlex
- W2094719314
- Cited by
- 169
- References
- 9
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 11 · 2023: 13 · 2022: 11 · 2021: 7 · 2020: 8 · 2019: 11 · 2018: 8 · 2017: 8 · 2016: 7 · 2015: 10 · 2014: 7 · 2013: 12 · 2012: 9
- FWCI
- 7.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropathology and Applied Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- remyelination, cuprizone, demyelination, corpus callosum, myelin basic protein, proteolipid protein, CNPase, myelin oligodendrocyte glycoprotein, oligodendrocyte differentiation, multiple sclerosis, immunohistochemical markers
- MeSH terms
- Animals, Corpus Callosum, Cuprizone, Demyelinating Diseases, Immunohistochemistry, Indoles, Male, Mice, Inbred C57BL, Monoamine Oxidase Inhibitors, Myelin Proteins, Nerve Fibers, Myelinated, Time, Microscopy, Electron, Transmission, Mice
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