Diverse Gene Expressions in the Prediction of Cuprizone-Induced Demyelination

Myelin abnormalities, oligodendrocyte damage, and concomitant glia activation are common characteristics of demyelinating diseases of the central nervous system. Administration of the neurotoxicant cuprizone (CPZ) has been extensively used to establish a reproducible mouse model of demyelination. However, its effects on myelin-related gene expression have not been sufficiently explored. In the present study, we used the Affymetrix Mouse Gene 2.0 ST Array to analyze the changes in gene expression profiles. Comparative gene expression profiling in age-matched C57BL/6 mice administered with 0.2% CPZ and with normal diet, revealed that the expression of 1655 genes was significantly changed in CPZ-fed mice with a fold change >= 1.5. Our results demonstrated that CPZ-induced demyelination induces apparent alterations in the expression of most of the myelin-related genes, including the 6 key genes MBP, MAG, and MOG and GFAP, CXCR4, and NgR, which were observed to be downregulated and upregulated, respectively, suggesting that the differences in gene expression in vivo could serve as potential therapeutic targets for remyelination.