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

Martin Meschkat, Anna M. Steyer, Marie-Theres Weil, Kathrin Kusch, Olaf Jahn, Lars Piepkorn, Paola Agüi-Gonzalez, Nhu Thi Ngoc Phan, Torben Ruhwedel, Boguslawa Sadowski, Silvio O. Rizzoli, Hauke B. Werner, Hannelore Ehrenreich, Klaus-Armin Nave and Wiebke Möbius ()
Additional contact information
Martin Meschkat: Max Planck Institute of Experimental Medicine
Anna M. Steyer: Max Planck Institute of Experimental Medicine
Marie-Theres Weil: Max Planck Institute of Experimental Medicine
Kathrin Kusch: Max Planck Institute of Experimental Medicine
Olaf Jahn: DFG Research Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB)
Lars Piepkorn: Max Planck Institute of Experimental Medicine
Paola Agüi-Gonzalez: University Medical Center Göttingen, Center for Biostructural Imaging of Neurodegeneration
Nhu Thi Ngoc Phan: University Medical Center Göttingen, Center for Biostructural Imaging of Neurodegeneration
Torben Ruhwedel: Max Planck Institute of Experimental Medicine
Boguslawa Sadowski: Max Planck Institute of Experimental Medicine
Silvio O. Rizzoli: DFG Research Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB)
Hauke B. Werner: Max Planck Institute of Experimental Medicine
Hannelore Ehrenreich: DFG Research Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB)
Klaus-Armin Nave: Max Planck Institute of Experimental Medicine
Wiebke Möbius: Max Planck Institute of Experimental Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-18

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-28720-y

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