Yu Qili, Hui Ryan, Park Jiyoung, Huang Yangyang, Kusnecov Alexander W, Dreyfus Cheryl F, Zhou Renping
Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 USA.
Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ 08854 USA.
Cell Biosci. 2017 Nov 3;7:59. doi: 10.1186/s13578-017-0181-3. eCollection 2017.
Multiple sclerosis (MS) is a severe neurological disorder, characterized by demyelination of the central nervous system (CNS), and with a prevalence of greater than 2 million people worldwide. In terms of research in MS pathology, the cuprizone toxicity model is widely used. Here we investigated the contribution of genetic differences in response to cuprizone-induced demyelination in two genetically different mouse strains: CD1 and C57BL/6.
We demonstrate that exposure to a diet containing 0.2% cuprizone resulted in less severe demyelination in the midline of the corpus callosum over the fornix in CD1 mice than C57BL/6 mice. With continuous cuprizone feeding, demyelination in CD1 mice was not prominent until after 7 weeks, in contrast to C57BL/6 mice, which showed prominent demyelination after 4 weeks of exposure. Concomitantly, immunohistochemical analysis demonstrated more oligodendrocytes, as well as fewer oligodendrocyte progenitor cells, microglia and astrocytes in cuprizone treated CD1 mice. We also analyzed 4-weeks-cuprizone treated corpus callosum tissue samples and found that cuprizone treated CD1 mice showed a smaller reduction of myelin-associated glycoprotein (MAG) and a smaller increase of Iba1 and NG2.
These observations suggest that CD1 mice are less vulnerable to cuprizone-induced demyelination than C57BL/6 mice and thus genetic background factors appear to influence the susceptibility to cuprizone-induced demyelination.
多发性硬化症（MS）是一种严重的神经系统疾病，其特征为中枢神经系统（CNS）脱髓鞘，全球患病率超过200万人。在MS病理学研究方面，铜螯合剂毒性模型被广泛应用。在此，我们研究了两种基因不同的小鼠品系CD1和C57BL/6对铜螯合剂诱导的脱髓鞘反应中基因差异的作用。
我们证明，与C57BL/6小鼠相比，给CD1小鼠喂食含0.2%铜螯合剂的饮食后，胼胝体中线穹窿上方的脱髓鞘程度较轻。持续喂食铜螯合剂后，CD1小鼠直到7周后脱髓鞘才明显，而C57BL/6小鼠在暴露4周后就出现了明显的脱髓鞘。同时，免疫组织化学分析显示，经铜螯合剂处理的CD1小鼠中少突胶质细胞更多，而少突胶质前体细胞、小胶质细胞和星形胶质细胞更少。我们还分析了经4周铜螯合剂处理的胼胝体组织样本，发现经铜螯合剂处理的CD1小鼠髓鞘相关糖蛋白（MAG）的减少幅度较小，Iba1和NG2的增加幅度也较小。
这些观察结果表明，CD1小鼠比C57BL/6小鼠对铜螯合剂诱导的脱髓鞘更不敏感，因此基因背景因素似乎会影响对铜螯合剂诱导脱髓鞘的易感性。
