Abstract
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.
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Data Availability
The microarray data obtained in this study have been deposited in the NCBI’s Gene Expression Omnibus (GEO) repository and are accessible through the GEO Series accession number GSE129049 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE129049). Other datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Acknowledgments
We would like to thank Prof. Tai Kyung Baik (Department of Anatomy and Neuroscience, Eulji University School of Medicine) for helpful discussion of the proposed illustration in this study.
Funding
This work was supported by the Mid-Career Researcher Program and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Government of Korea (2016R1A2B4007413, 2017R1A2B4002405, 2017R1A2B1006373, 2019R1A2C2083947, 2017R1D1A1B03031502).
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Han, S.R., Kang, Y.H., Yoo, SM. et al. Diverse Gene Expressions in the Prediction of Cuprizone-Induced Demyelination. Neurotox Res 37, 732–742 (2020). https://doi.org/10.1007/s12640-019-00154-3
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DOI: https://doi.org/10.1007/s12640-019-00154-3