AUTHOR=Joost Sarah , Schweiger Felix , Pfeiffer Friederike , Ertl Carolin , Keiler Jonas , Frank Marcus , Kipp Markus 

TITLE=Cuprizone Intoxication Results in Myelin Vacuole Formation

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=16

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2022.709596

DOI=10.3389/fncel.2022.709596

ISSN=1662-5102

ABSTRACT=<p>Myelin damage is a histopathological hallmark of multiple sclerosis lesions. Results of <italic>post mortem</italic> studies suggest that impaired myelin-axon interaction characterized by focal myelin detachments is an early event during lesion genesis. In this study, we investigated the ultrastructural changes of the axon-myelin interface in the cuprizone model using serial block face scanning electron microscopy and immunohistochemistry. We show that non-inflammatory injury of oligodendrocytes by cuprizone intoxication results in myelin vacuole formation and axonal swellings, paralleled by early alterations of the node of Ranvier cytoarchitecture. This remarkable resemblance of ultrastructural myelin characteristics in multiple sclerosis and the cuprizone animal model suggests that the cuprizone model is a valuable tool to study early pathologies during lesion formation.</p>