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Metabolism and gene expression during cuprizone‐induced demyelination/remyelination
Author(s) -
Morell P.,
Jurevics H.,
Largent C.,
Hostettler J.,
Sammond D.,
Matsushima G.,
Toews A.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.81.s1.16_2.x
Subject(s) - remyelination , myelin , cerebroside , corpus callosum , biology , gene expression , microglia , white matter , multiple sclerosis , microbiology and biotechnology , gene , neuroscience , central nervous system , immunology , biochemistry , medicine , inflammation , radiology , magnetic resonance imaging
Exposure of mice to the copper chelator, Cuprizone, results in a CNS demyelination; remyelination occurs following removal of this metabolic insult. Using this model, we have demonstrated changes in content and metabolism of myelin lipids in whole brain. We now extend these biochemical studies to brain regions and identify corpus callosum as particularly severely affected; 65% of cerebroside is lost after 6 weeks of exposure. Animals can be rescued by removal of the toxicant and the extent of recovery of myelin, as well as recovery of ability to synthesize cerebroside and cholesterol, can be determined. The temporal pattern for concentration of myelin basic protein tracked that of cerebroside, supporting the assumption that cerebroside level is a good surrogate for myelin concentration. We also applied Affymetrix microarray technology to corpus callosum to track temporal changes in steady‐state levels of mRNA species related to demyelination and remyelination. Genes coding for myelin structural components were greatly down‐regulated during demyelination and up‐regulated during remyelination. Genes related to microglia/macrophages appeared in a time course (peaking at 6 weeks) correlating with that expected for phagocytosis of myelin. mRNAs coding for many cytokine genes had peak expression at 4 weeks, compatible with an intercellular signaling role. Of interest were other genes with temporal patterns correlating with one of the three patterns mentioned above, but with functions not obviously related to demyelination/remyelination. The ability to correlate gene expression with known pathophysiological and regenerative events should be of utility in elucidating further function of such genes. Acknowledgements: Supported by USPHS & NMSS grants.