Focused ion beam-scanning electron microscopy links pathological myelin outfoldings to axonal changes in mice lacking Plp1 or Mag

Steyer, A. M. et al. (2023) Focused ion beam-scanning electron microscopy links pathological myelin outfoldings to axonal changes in mice lacking Plp1 or Mag. Glia, 71(3), pp. 509-523. (doi: 10.1002/glia.24290) (PMID:36354016)

Abstract

Healthy myelin sheaths consist of multiple compacted membrane layers closely encasing the underlying axon. The ultrastructure of CNS myelin requires specialized structural myelin proteins, including the transmembrane-tetraspan proteolipid protein (PLP) and the Ig-CAM myelin-associated glycoprotein (MAG). To better understand their functional relevance, we asked to what extent the axon/myelin-units display similar morphological changes if PLP or MAG are lacking. We thus used focused ion beam-scanning electron microscopy (FIB-SEM) to re-investigate axon/myelin-units side-by-side in Plp- and Mag-null mutant mice. By three-dimensional reconstruction and morphometric analyses, pathological myelin outfoldings extend up to 10 μm longitudinally along myelinated axons in both models. More than half of all assessed outfoldings emerge from internodal myelin. Unexpectedly, three-dimensional reconstructions demonstrated that both models displayed complex axonal pathology underneath the myelin outfoldings, including axonal sprouting. Axonal anastomosing was additionally observed in Plp-null mutant mice. Importantly, normal-appearing axon/myelin-units displayed significantly increased axonal diameters in both models according to quantitative assessment of electron micrographs. These results imply that healthy CNS myelin sheaths facilitate normal axonal diameters and shape, a function that is impaired when structural myelin proteins PLP or MAG are lacking.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Edgar, Professor Julia
• Authors: Steyer, A. M., Buscham, T. J., Lorenz, C., Hümmert, S., Eichel-Vogel, M. A., Schadt, L. C., Edgar, J. M., Köster, S., Möbius, W., Nave, K.-A., and Werner, H. B.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Research Centre: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology
• Journal Name: Glia
• Publisher: Wiley
• ISSN: 0894-1491
• ISSN (Online): 1098-1136
• Published Online: 10 November 2022
• Copyright Holders: Copyright © 2022 The Author
• First Published: First published in Glia 71(3):509-523
• Publisher Policy: Reproduced under a Creative Commons licence