Nature Communications: White matter integrity in mice requires continuous myelin synthesis at the inner tongue
Congratulation to Dr. Wiebke Möbius and her team for the excellent publication!
In our publication we describe how we discovered that a stable structure like a myelin is slowly and continuously turned over by addition of newly synthetized components at the inner tongue of the myelin sheath. For this purpose, we knocked out myelin basic protein (MBP) in adult mice and observed how the myelin sheaths change their structure over time. For visualization we applied advanced imaging techniques using transmission electron microscopy (A-D) and 3D reconstruction based on image stacks obtained by focused ion beam-scanning electron microscopy (FIB-SEM, E).
Source: Meschkat et al. (2022) Nature Communications 13:1163 | https://doi.org/10.1038/s41467-022-28720-ywww.nature.com/naturecommunications
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.
Meschkat, M., Steyer, A.M., Weil, MT. et al. White matter integrity in mice requires continuous myelin synthesis at the inner tongue. Nat Commun 13, 1163 (2022). https://doi.org/10.1038/s41467-022-28720-ys41467-022-28720-y