Strain differences in cuprizone induced demyelination

Qili Yu,Ryan Hui,Jiyoung Park,Renping Zhou,Yangyang Huang,Alexander W Kusnecov,Cheryl F Dreyfus

doi:10.1186/s13578-017-0181-3

Qili Yu, Ryan Hui + Show 5 more

Open Access

https://doi.org/10.1186/s13578-017-0181-3

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Abstract

BackgroundMultiple 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.ResultsWe 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.ConclusionsThese 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.

Highlights

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
An alternative histological approach that is complementary to the Black gold staining is the Luxol fast blue–periodic acid Schiff (LFB–PAS) method, which stains the myelin and stains the demyelinated areas in pink, providing a counter stain to contrast with the positive myelin stain
By 7 weeks, CD1 mice were slightly less demyelinated compared to C57BL/6 mice, but this difference is not statistically significant, the Black gold data shows CD1 mice still exhibit more Black gold-stained fibers at this point

Summary

Introduction

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. We investigated the contribution of genetic differences in response to cuprizone-induced demyelination in two genetically different mouse strains: CD1 and C57BL/6. Multiple sclerosis (MS) is a chronic, demyelinating disease in which the myelin sheath, the insulating cover that wraps around axons of neurons, is damaged. Most investigators use the standard C57BL/6 mouse strain in the cuprizone model to study the different molecular components involved in the complex pathogenic processes leading to corpus callosum demyelination [5]. It is important to know the relative sensitivity of different mouse strains in response to cuprizone toxicity. By comparing it to the C57BL/6 strain, we show that CD1 mice are less vulnerable to cuprizone-induced demyelination in the corpus callosum. Genetic differences greatly influence the susceptibility of mice to cuprizone-induced damage, and that the influence of

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