Cuprizone Intoxication Results in Myelin Vacuole Formation

Sarah Joost; Felix Schweiger; Friederike Pfeiffer; Carolin Ertl; Jonas Keiler; Marcus Frank; Markus Kipp

doi:10.3389/fncel.2022.709596

Cuprizone Intoxication Results in Myelin Vacuole Formation

Front Cell Neurosci. 2022 Feb 18:16:709596. doi: 10.3389/fncel.2022.709596. eCollection 2022.

Authors

Sarah Joost¹, Felix Schweiger¹, Friederike Pfeiffer², Carolin Ertl¹, Jonas Keiler¹, Marcus Frank^{3

4}, Markus Kipp^{1

5}

Affiliations

¹ Institute of Anatomy, Rostock University Medical Center, Rostock, Germany.
² Werner Reichardt Centre for Integrative Neuroscience, University of Tübingen, Tübingen, Germany.
³ Medical Biology and Electron Microscopy Center, Rostock University Medical Center, Rostock, Germany.
⁴ Department of Life, Light and Matter, University of Rostock, Rostock, Germany.
⁵ Center for Transdisciplinary Neurosciences Rostock, Rostock University Medical Center, Rostock, Germany.

Abstract

Myelin damage is a histopathological hallmark of multiple sclerosis lesions. Results of post mortem 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.

Keywords: multiple sclerosis; myelin pathology; myelin ultrastructure; myelin-axon interaction; oligodendrocyte injury; serial block face scanning electron microscopy; vacuoles.