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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., et al. (2022). White matter integrity in mice requires continuous myelin synthesis at the inner tongue. Nature Communications, 13: 1163. doi:10.1038/s41467-022-28720-y.

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Meschkat, M.1, Author              
Steyer, A. M.1, Author              
Weil, M.-T.1, Author              
Kusch, K.1, Author              
Jahn, O.2, Author              
Piepkorn, L.2, Author              
Agüi-Gonzalez, P., Author
Phan, N. T. N., Author
Ruhwedel, T.1, Author              
Sadowski, B.1, Author              
Rizzoli, S. O., Author
Werner, H. B.1, Author
Ehrenreich, H.3, Author              
Nave, K.-A.1, Author              
Möbius, W.1, Author              
Affiliations:
1Department of Neurogenetics, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society, ou_3350301              
2Department of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society, ou_3350300              
3Research Group of Clinical Neuroscience, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society, ou_3350303              

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 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 experi- mentally 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.

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Language(s): eng - English
 Dates: 2022-03-04
 Publication Status: Published online
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 Rev. Type: Peer
 Identifiers: DOI: 10.1038/s41467-022-28720-y
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Title: Nature Communications
Source Genre: Journal
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Pages: 18 Volume / Issue: 13 Sequence Number: 1163 Start / End Page: - Identifier: -