Microglia regulate central nervous system myelin growth and integrity

Abstract: Myelin is required for the function of neuronal axons in the central nervous system, but the mechanisms that support myelin health are unclear. Although macrophages in the central nervous system have been implicated in myelin health, it is unknown which macrophage populations are involved and which aspects they influence. Here we show that resident microglia are crucial for the maintenance of myelin health in adulthood in both mice and humans. We demonstrate that microglia are dispensable for developmental myelin ensheathment. However, they are required for subsequent regulation of myelin growth and associated cognitive function, and for preservation of myelin integrity by preventing its degeneration. We show that loss of myelin health due to the absence of microglia is associated with the appearance of a myelinating oligodendrocyte state with altered lipid metabolism. Moreover, this mechanism is regulated through disruption of the TGFβ1–TGFβR1 axis. Our findings highlight microglia as promising therapeutic targets for conditions in which myelin growth and integrity are dysregulated, such as in ageing and neurodegenerative disease

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch
Anmerkungen
Nature. - 613, 7942 (2023) , 120-129, ISSN: 1476-4687

Ereignis
Veröffentlichung
(wo)
Freiburg
(wer)
Universität
(wann)
2022
Urheber
McNamara, Niamh B.
Amann, Lukas
Prinz, Marco
Priller, Josef
Miron, Veronique E.

DOI
10.1038/s41586-022-05534-y
URN
urn:nbn:de:bsz:25-freidok-2322457
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
25.03.2025, 13:44 MEZ

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  • 2022

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