Nat. Commun. 13, 1163 (2022)
Myelin insulates axons and facilitates electrical conduction along the axons. Most myelin is formed by oligodendrocytes during development of the nervous system, but it is continuously and slowly exchanged and renewed. A recent paper by Meschkat, Möbius and colleagues sheds light on how this myelin turnover in adulthood occurs. The authors generated a mouse line with a floxed exon 1 of the gene encoding MBP (an abundant myelin-associated protein), which they crossed with the oligodendrocyte-specific inducible Plp-CreERT2 reporter mouse line to block MBP synthesis in oligodendrocytes, and then investigated the effects on the stability of compact myelin sheaths. Mbp ablation induced in two-month-old mice resulted in demyelination without affecting oligodendrocyte survival. Analysis of the proteome of the optic nerve of these mice revealed that Mbp ablation leads to progressively decreased expression of myelin proteins and proteins involved in axon–myelin interaction and myelin lipid synthesis; similar changes were observed in shiverer mice, a model of myelin deficiency. The loss of MBP in the Cre-inducible mice resulted in loss of compact myelin and did not affect oligodendrocyte survival, which enabled the authors to investigate the morphological changes that occur during myelin turnover. Structural high-resolution imaging of different CNS white-matter tracts of wild-type and transgenic mice showed that the paranodal and juxtaparanodal region at the inner tongue (the leading edge of the myelin sheath in direct contact with the axon) is an important site for myelin renewal in adult mice. Microglia and astrocytes are involved in myelin removal; however, the data suggested that myelin may also be removed in the form of myelinoid bodies abaxonally and in the inner tongue. In summary, Meschkat, Möbius and colleagues propose that white-matter integrity requires a process of myelin turnover and renewal in adulthood in which newly synthesized myelin membrane is incorporated at the inner tongue.
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