Abstract
Demyelination induced by cuprizone in mice has served a useful model system for the study of demyelinating diseases, such as multiple sclerosis. Severity of demyelination by cuprizone, however, varies across different regions of the central nervous system; the corpus callosum is sensitive, while the optic nerves are resistant. Here, we investigated the effects of cuprizone on optic nerves, focusing on the axo-glial junctions. Immunostaining for sodium channels, contactin-associated protein, neurofascins, and potassium channels revealed that there were no massive changes in the density and morphology of the axo-glial junctions in cuprizone-treated optic nerves. However, when we counted the number of incomplete junctional complexes, we observed increased numbers of isolated paranodes. These isolated paranodes were immunopositive for both axonal and glial membrane proteins, indicating that they were the contact sites between axons and glia. These were not associated with sodium channels or potassium channels, suggesting the absence of physiological functions. When teased axons from cuprizone-treated optic nerves were immunostained, the isolated paranodes were found at the internode region of the myelin. From these observations, we conclude that cuprizone induces new contacts between axons and myelins at the internode region.
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Acknowledgements
We thank Ms. Hiroko Suzuki, Mr. Minoru Kato, and Mr. Hitoshi Nagai at Mitsubishi Tanabe Pharma Corporation for introducing us to this research field, supplying us some antibodies, and valuable contributions to discussions on the demyelination in animal models.
Funding
This study was funded by the Japanese Society for the Promotion of Science (JSPS KAKENHI Grant Number JP17K07083).
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Kojima, W., Hayashi, K. Changes in the axo-glial junctions of the optic nerves of cuprizone-treated mice. Histochem Cell Biol 149, 529–536 (2018). https://doi.org/10.1007/s00418-018-1654-0
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DOI: https://doi.org/10.1007/s00418-018-1654-0