Myelin insulation as a risk factor for axonal degeneration in autoimmune demyelinating disease

  • Axonal degeneration determines the clinical outcome of multiple sclerosis and is thought to result from exposure of denuded axons to immune-mediated damage. Therefore, myelin is widely considered to be a protective structure for axons in multiple sclerosis. Myelinated axons also depend on oligodendrocytes, which provide metabolic and structural support to the axonal compartment. Given that axonal pathology in multiple sclerosis is already visible at early disease stages, before overt demyelination, we reasoned that autoimmune inflammation may disrupt oligodendroglial support mechanisms and hence primarily affect axons insulated by myelin. Here, we studied axonal pathology as a function of myelination in human multiple sclerosis and mouse models of autoimmune encephalomyelitis with genetically altered myelination. We demonstrate that myelin ensheathment itself becomes detrimental for axonal survival and increases the risk of axons degenerating in an autoimmune environment. ThisAxonal degeneration determines the clinical outcome of multiple sclerosis and is thought to result from exposure of denuded axons to immune-mediated damage. Therefore, myelin is widely considered to be a protective structure for axons in multiple sclerosis. Myelinated axons also depend on oligodendrocytes, which provide metabolic and structural support to the axonal compartment. Given that axonal pathology in multiple sclerosis is already visible at early disease stages, before overt demyelination, we reasoned that autoimmune inflammation may disrupt oligodendroglial support mechanisms and hence primarily affect axons insulated by myelin. Here, we studied axonal pathology as a function of myelination in human multiple sclerosis and mouse models of autoimmune encephalomyelitis with genetically altered myelination. We demonstrate that myelin ensheathment itself becomes detrimental for axonal survival and increases the risk of axons degenerating in an autoimmune environment. This challenges the view of myelin as a solely protective structure and suggests that axonal dependence on oligodendroglial support can become fatal when myelin is under inflammatory attack.show moreshow less

Download full text files

Export metadata

Statistics

Number of document requests

Additional Services

Share in Twitter Search Google Scholar
Metadaten
Author:Erik Schäffner, Mar Bosch-Queralt, Julia M. Edgar, Maria Lehning, Judith Strauß, Niko Fleischer, Theresa Kungl, Peter WieghoferGND, Stefan A. Berghoff, Tilo Reinert, Martin Krueger, Markus Morawski, Wiebke Möbius, Alonso Barrantes-Freer, Jens Stieler, Ting Sun, Gesine Saher, Markus H. Schwab, Christoph Wrede, Maximilian Frosch, Marco Prinz, Daniel S. Reich, Alexander Flügel, Christine Stadelmann, Robert Fledrich, Klaus-Armin Nave, Ruth M. Stassart
URN:urn:nbn:de:bvb:384-opus4-1068324
Frontdoor URLhttps://opus.bibliothek.uni-augsburg.de/opus4/106832
ISSN:1097-6256OPAC
ISSN:1546-1726OPAC
Parent Title (English):Nature Neuroscience
Publisher:Springer Science and Business Media LLC
Type:Article
Language:English
Year of first Publication:2023
Publishing Institution:Universität Augsburg
Release Date:2023/08/18
Tag:General Neuroscience
Volume:26
Issue:7
First Page:1218
Last Page:1228
DOI:https://doi.org/10.1038/s41593-023-01366-9
Institutes:Medizinische Fakultät
Medizinische Fakultät / Professur für Zelluläre Neuroanatomie
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):CC-BY 4.0: Creative Commons: Namensnennung (mit Print on Demand)