Median eminence myelin continuously turns over in adult mice

ABSTRACTObjectiveOligodendrocyte progenitor cell differentiation is regulated by nutritional signals in the adult median eminence (ME), but the consequences on local myelination are unknown. The aim of this study was to characterise myelin plasticity in the ME of adult mice in health or in response to chronic nutritional challenge.MethodsWe assessed new oligodendrocyte and myelin generation and stability in the ME of healthy adult male mice using bromodeoxyuridine labelling and genetic fate mapping tools. We assessed the contribution of microglia to ME myelin plasticity in PLX5622-treated C57BL6/J mice and inPdgfra-Cre/ERT2;R26R-eYFP;Myrffl/flmice, where adult oligodendrogenesis is genetically blunted. Finally, we investigated how 45% high fat diet or 70% caloric restriction feeding paradigms impact ME oligodendrocyte lineage progression and myelination in C57BL6/J mice.ResultsWe show that myelinating oligodendrocytes (OLs) are continuously and rapidly generated in the adult ME. Paradoxically, OL number and myelin amounts remain remarkably stable in the adult ME. In fact, the high rate of new OL and myelin generation in the ME is offset by continuous turnover of both. We show that microglia are required for continuous OL and myelin production, and that ME myelin plasticity regulates the recruitment of local immune cells. Finally, we provide evidence that ME myelination is regulated by the body’s energetic status, decreased in calorie-restricted animals, and increased in mice fed a high fat diet.ConclusionsThis study uncovers a previously unappreciated form of ME structural plasticity and mechanism of myelin remodeling in the adult brain.