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Myelin insulation as a risk factor for axonal degeneration in autoimmune demyelinating disease
E Schäffner, JM Edgar, M Lehning, J Strauß, M Bosch-Queralt, P Wieghofer, SA Berghoff, M Krueger, M Morawski, T Reinert, W Möbius, A Barrantes-Freer, M Prinz, DS Reich, A Flügel, C. Stadelmann, R Fledrich, RM Stassart, KA Nave
doi: https://doi.org/10.1101/2021.11.11.468223
E Schäffner
1Department of Neurogenetics, Max-Planck-Institute of Experimental Medicine, Göttingen, Germany
2Paul-Flechsig-Institute of Neuropathology, University Clinic Leipzig, Leipzig, German
JM Edgar
1Department of Neurogenetics, Max-Planck-Institute of Experimental Medicine, Göttingen, Germany
3Institute of Infection, Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom
M Lehning
2Paul-Flechsig-Institute of Neuropathology, University Clinic Leipzig, Leipzig, German
J Strauß
4Institute of Neuroimmunology, University Medical Center Göttingen, Göttingen, Germany
M Bosch-Queralt
2Paul-Flechsig-Institute of Neuropathology, University Clinic Leipzig, Leipzig, German
P Wieghofer
5Institute of Anatomy, Leipzig University, Leipzig, Germany
6Cellular Neuroanatomy, Institute of Theoretical Medicine, Medical Faculty, University of Augsburg, Augsburg, Germany
SA Berghoff
1Department of Neurogenetics, Max-Planck-Institute of Experimental Medicine, Göttingen, Germany
7German Center for Neurodegenerative Diseases (DZNE), Munich, Germany
M Krueger
5Institute of Anatomy, Leipzig University, Leipzig, Germany
M Morawski
8Paul-Flechsig-Institute of Brain Research, Leipzig University, Leipzig, Germany
T Reinert
2Paul-Flechsig-Institute of Neuropathology, University Clinic Leipzig, Leipzig, German
9Department of Neurophysics, Max-Planck-Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
W Möbius
1Department of Neurogenetics, Max-Planck-Institute of Experimental Medicine, Göttingen, Germany
A Barrantes-Freer
2Paul-Flechsig-Institute of Neuropathology, University Clinic Leipzig, Leipzig, German
M Prinz
10Institute of Neuropathology, Medical Faculty, University of Freiburg, Freiburg, Germany
11Centre for NeuroModulation (NeuroModBasics), University of Freiburg, Freiburg, Germany
12Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany
DS Reich
13Translational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
A Flügel
4Institute of Neuroimmunology, University Medical Center Göttingen, Göttingen, Germany
C. Stadelmann
14Institute of Neuropathology, University Medical Center Göttingen, Göttingen, Germany
R Fledrich
1Department of Neurogenetics, Max-Planck-Institute of Experimental Medicine, Göttingen, Germany
5Institute of Anatomy, Leipzig University, Leipzig, Germany
RM Stassart
1Department of Neurogenetics, Max-Planck-Institute of Experimental Medicine, Göttingen, Germany
2Paul-Flechsig-Institute of Neuropathology, University Clinic Leipzig, Leipzig, German
KA Nave
1Department of Neurogenetics, Max-Planck-Institute of Experimental Medicine, Göttingen, Germany
Abstract
Axonal degeneration determines the clinical outcome of multiple sclerosis (MS), and is thought to result from exposure of denuded axons to immune-mediated damage. We challenge this view after finding in MS and its mouse models that myelin itself increases the risk of axons to degenerate under inflammatory conditions. We propose a model for demyelinating diseases in which for axons that remain myelinated, and thus shielded from the extracellular milieu, dependence from oligodendroglial support turns fatal in an autoimmune disease environment.
Competing Interest Statement
The authors have declared no competing interest.
Copyright
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Posted November 13, 2021.
Myelin insulation as a risk factor for axonal degeneration in autoimmune demyelinating disease
E Schäffner, JM Edgar, M Lehning, J Strauß, M Bosch-Queralt, P Wieghofer, SA Berghoff, M Krueger, M Morawski, T Reinert, W Möbius, A Barrantes-Freer, M Prinz, DS Reich, A Flügel, C. Stadelmann, R Fledrich, RM Stassart, KA Nave
bioRxiv 2021.11.11.468223; doi: https://doi.org/10.1101/2021.11.11.468223
Myelin insulation as a risk factor for axonal degeneration in autoimmune demyelinating disease
E Schäffner, JM Edgar, M Lehning, J Strauß, M Bosch-Queralt, P Wieghofer, SA Berghoff, M Krueger, M Morawski, T Reinert, W Möbius, A Barrantes-Freer, M Prinz, DS Reich, A Flügel, C. Stadelmann, R Fledrich, RM Stassart, KA Nave
bioRxiv 2021.11.11.468223; doi: https://doi.org/10.1101/2021.11.11.468223
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