Gene Expression in Brain during Cuprizone-Induced Demyelination and Remyelination
Abstract
When C57BL/6J mice, 8 weeks of age, received 0.2% Cuprizone in their diet, extensive demyelination in corpus callosum was detectable after 3 weeks, and there was massive demyelination by 4 weeks. As expected, the accumulation of phagocytically active microglia/macrophages correlated closely with demyelination. When Cuprizone was removed from the diet, remyelination was soon initiated; after 6 weeks of recovery, myelin levels were near-normal and phagocytic cells were no longer prominent. Steady-state levels of mRNA for myelin-associated glycoprotein, myelin basic protein, and ceramide galactosyltransferase were already profoundly depressed after 1 week of Cuprizone exposure and were only 10-20% of control values after 2 weeks. Unexpectedly, upregulation of mRNA for these myelin genes did not correlate with initiation of remyelination but rather with accumulation of microglia/macrophages. After 6 weeks of exposure to Cuprizone, mRNA levels were at control levels or higher-in the face of massive demyelination. This suggests that in addition to effecting myelin removal, microglia/macrophages may simultaneously push surviving oligodendroglia or their progenitors toward myelination.
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C57BL/6 mice showed greater than 50% remyelination within 2 weeks of discontinuation of cuprizone.
“C57BL/6 mice showed greater than 50% remyelination within 2 weeks of discontinuation of cuprizone 2, 42, which is in stark contrast to the reduced remyelination reported here for SJL.”
From SJL Mice Exposed to Cuprizone Intoxication Reveal Strain and Gender Pattern Differences in Demyelination (2009) · cites this paper as [42]
CGT and HMG-CoA reductase are reduced following cuprizone consumption.
“Ceramide galactosyltransferase (CGT) and β-Hydroxy β-methylglutaryl-CoA (HMG-CoA) reductase are two enzymes that are reduced following cuprizone consumption [159, 160].”
From Oligodendrocyte death and myelin loss in the cuprizone model: an updated overview of the intrinsic and extrinsic causes of cuprizone demyelination (2022) · cites this paper as [159]
The mRNA of myelin proteins such as MAG and MBP decreases in the first week after cuprizone diet in rats by approximately 75% and 50% respectively.
“For example, Morell and colleagues found that the messenger ribonucleic acid (mRNA) of various myelin proteins, such as MAG and myelin basic protein (MBP), decreases in the first week after cuprizone diet in rats by ~ 75% and ~ 50% respectively [159, 160].”
From Oligodendrocyte death and myelin loss in the cuprizone model: an updated overview of the intrinsic and extrinsic causes of cuprizone demyelination (2022) · cites this paper as [159]
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References 40 · Cited by 213
- Authors
- Morell, P., Barrett, C. V., Mason, J. L., Toews, A. D., Hostettler, J. D., Knapp, G. W., & Matsushima, G. K.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Matsushima, G.K.
- Venue
- Molecular and Cellular Neuroscience
- Publisher
- Elsevier BV
- Published
- 1998-11
- Volume
- 12
- Issue
- 4-5
- Pages
- 220-227
- ISSN
- 1044-7431 (ISSN-L)
- OpenAlex
- W2012724257
- Cited by
- 213
- References
- 40
- Citations by year
- 2026: 5 · 2024: 6 · 2023: 5 · 2022: 11 · 2021: 10 · 2020: 9 · 2019: 18 · 2018: 7 · 2017: 10 · 2016: 5 · 2015: 7 · 2014: 7 · 2013: 7 · 2012: 9
- FWCI
- 3.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular and Cellular Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ns011615-29, 5r29ns035372-05, 5p01es001104-21)
- National Institute of Neurological Disorders and Stroke (NS-11615, NS-35372)
- National Institute of Environmental Health Sciences (ES-01104)
- 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
- cuprizone, demyelination, remyelination, microglia/macrophages, myelin-associated glycoprotein, myelin basic protein, myelin gene expression, oligodendrocytes, corpus callosum, demyelinating disease
- MeSH terms
- Animals, Brain, Corpus Callosum, Cuprizone, Demyelinating Diseases, Diet, Myelin Basic Protein, Galactosyltransferases, Gene Expression Regulation, Macrophages, Mice, Inbred C57BL, Myelin Proteins, Myelin Sheath, Phagocytosis, RNA, Messenger, Transcription, Genetic, Microglia, Myelin-Associated Glycoprotein, N-Acylsphingosine Galactosyltransferase, Mice
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