Microglia regulate myelin growth and integrity in the central nervous system

Niamh McNamara, David Munro, Nadine Bestard-Cuche, Akiko Uyeda, Jeroen F J Bogie, Alana Hoffmann, Rebecca Holloway, Irene Molina-Gonzalez, Katie Askew, Stephen Mitchell, William Mungall, Michael Dodds, Carsten Dittmayer, Jon Moss, Jamie Rose, Stefan Szymkowiak, Lukas Amann, Barry W McColl, Marco Prinz, Tara Spires-JonesWerner Stenzel, Karen Horsburgh, Jerome J A Hendriks, Clare Pridans, Rieko Muramatsu, Anna C Williams, Josef Priller, Véronique E Miron*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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 health1, 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 disease2,3.
Original languageEnglish
Pages (from-to)120-129
Early online date14 Dec 2022
Publication statusPublished - 5 Jan 2023


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