RT Journal Article
SR Electronic
T1 White matter integrity requires continuous myelin synthesis at the inner tongue
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.09.02.279612
DO 10.1101/2020.09.02.279612
A1 Martin Meschkat
A1 Anna M. Steyer
A1 Marie-Theres Weil
A1 Kathrin Kusch
A1 Olaf Jahn
A1 Lars Piepkorn
A1 Paola Agüi-Gonzalez
A1 Nhu Thi Ngoc Phan
A1 Torben Ruhwedel
A1 Boguslawa Sadowski
A1 Silvio O. Rizzoli
A1 Hauke B. Werner
A1 Hannelore Ehrenreich
A1 Klaus-Armin Nave
A1 Wiebke Möbius
YR 2020
UL http://biorxiv.org/content/early/2020/09/03/2020.09.02.279612.abstract
AB Myelin, the electrically insulating axonal sheath, is composed of lipids and proteins with exceptionally long lifetime. This raises the question how myelin function is affected by myelin turnover. We have studied 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 survived recombination, continued expressing myelin genes, but failed to maintain compacted myelin sheaths. Using 3D electron microscopy and mass spectrometry imaging we visualized myelin-like membranes that failed to incorporate adaxonally, most prominently at juxta-paranodes. Myelinoid body formation indicated degradation of existing myelin at the abaxonal side and at the inner tongue of the sheath. Compacted myelin thinning and shortening of internodes, with about 50% myelin lost after 20 weeks (=5 months), ultimately led to axonal pathology and neurological disease. These data reveal that functional axon-myelin units require the continuous incorporation of new myelin membranes.Competing Interest StatementThe authors have declared no competing interest.