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

2023 | journal article. A publication with affiliation to the University of Göttingen.

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​Myelin insulation as a risk factor for axonal degeneration in autoimmune demyelinating disease​
Schäffner, E.; Bosch-Queralt, M.; Edgar, J. M.; Lehning, M.; Strauß, J.; Fleischer, N. & Kungl, T. et al.​ (2023) 
Nature Neuroscience,.​ DOI: 

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Schäffner, Erik; Bosch-Queralt, Mar; Edgar, Julia M.; Lehning, Maria; Strauß, Judith; Fleischer, Niko; Kungl, Theresa; Wieghofer, Peter; Berghoff, Stefan A.; Reinert, Tilo; Stassart, Ruth M.
Abstract 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. 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.
Issue Date
Nature Neuroscience 
EXC 2067: Multiscale Bioimaging 
TRR 274: Checkpoints of Central Nervous System Recovery 
TRR 274 | A03: Checkpoints determining recovery from acute autoimmune CNS grey matter lesions 
TRR 274 | C01: Oligodendroglial NMDA receptors and NMDAR1 autoantibodies as determinants of axonal integrity in neuropsychiatric disease 
Working Group
RG Möbius 
RG Stadelmann-Nessler 
RG Bodenschatz (Laboratory for Fluid Physics, Pattern Formation and Biocomplexity) 
RG Nave (Neurogenetics) 
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