White matter integrity in mice requires continuous myelin synthesis at the inner tongue

2022 | journal article; research paper. A publication with affiliation to the University of Göttingen.

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​White matter integrity in mice requires continuous myelin synthesis at the inner tongue​
Meschkat, M.; Steyer, A. M.; Weil, M.-T.; Kusch, K. ; Jahn, O. ; Piepkorn, L. & Agüi-Gonzalez, P.  et al.​ (2022) 
Nature Communications13(1) art. 1163​.​ DOI: https://doi.org/10.1038/s41467-022-28720-y 

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Meschkat, Martin; Steyer, Anna M.; Weil, Marie-Theres; Kusch, Kathrin ; Jahn, Olaf ; Piepkorn, Lars; Agüi-Gonzalez, Paola ; Phan, Nhu Thi Ngoc ; Ruhwedel, Torben; Sadowski, Boguslawa ; Möbius, Wiebke 
Abstract Myelin, the electrically insulating sheath on axons, undergoes dynamic changes over time. However, it is composed of proteins with long lifetimes. This raises the question how such a stable structure is renewed. Here, we study the integrity of myelinated tracts after experimentally preventing the formation of new myelin in the CNS of adult mice, using an inducible Mbp null allele. Oligodendrocytes survive recombination, continue to express myelin genes, but they fail to maintain compacted myelin sheaths. Using 3D electron microscopy and mass spectrometry imaging we visualize myelin-like membranes failing to incorporate adaxonally, most prominently at juxta-paranodes. Myelinoid body formation indicates degradation of existing myelin at the abaxonal side and the inner tongue of the sheath. Thinning of compact myelin and shortening of internodes result in the loss of about 50% of myelin and axonal pathology within 20 weeks post recombination. In summary, our data suggest that functional axon-myelin units require the continuous incorporation of new myelin membranes.
Issue Date
Nature Communications 
EXC 2067: Multiscale Bioimaging 
FOR 2848: Architektur und Heterogenität der inneren mitochondrialen Membran auf der Nanoskala 
FOR 2848 | P08: Strukturelle und funktionale Veränderungen der inneren mitochondrialen Membran axonaler Mitochondrien in vivo in einem dymyelinisierenden Mausmodell 
TRR 274: Checkpoints of Central Nervous System Recovery 
TRR 274 | C01: Oligodendroglial NMDA receptors and NMDAR1 autoantibodies as determinants of axonal integrity in neuropsychiatric disease 
Working Group
RG Möbius 
RG Rizzoli (Quantitative Synaptology in Space and Time) 
RG Ehrenreich (Clinical Neuroscience) 
RG Nave (Neurogenetics) 



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