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Microglia regulate central nervous system myelin growth and integrity.

Nature (2022-12-15)
Niamh B McNamara, David A D Munro, Nadine Bestard-Cuche, Akiko Uyeda, Jeroen F J Bogie, Alana Hoffmann, Rebecca K Holloway, Irene Molina-Gonzalez, Katharine E Askew, Stephen Mitchell, William Mungall, Michael Dodds, Carsten Dittmayer, Jonathan Moss, Jamie Rose, Stefan Szymkowiak, Lukas Amann, Barry W McColl, Marco Prinz, Tara L Spires-Jones, Werner Stenzel, Karen Horsburgh, Jerome J A Hendriks, Clare Pridans, Rieko Muramatsu, Anna Williams, Josef Priller, Veronique E Miron
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 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.

MATERIALS
Product Number
Brand
Product Description

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