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

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

Nature communications (2022-03-06)
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, Wiebke Möbius
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-APP A4 Antibody, a.a. 66-81 of APP {NT}, clone 22C11, clone 22C11, Chemicon®, from mouse
Sigma-Aldrich
Anti-Luteinizing Hormone Releasing Hormone Antibody, serum, Chemicon®