TY - JOUR
T1 - Microglia regulate myelin growth and integrity in the central nervous system
AU - McNamara, Niamh
AU - Munro, David
AU - Bestard-Cuche, Nadine
AU - Uyeda, Akiko
AU - Bogie, Jeroen F J
AU - Hoffmann, Alana
AU - Holloway, Rebecca
AU - Molina-Gonzalez, Irene
AU - Askew, Katie
AU - Mitchell, Stephen
AU - Mungall, William
AU - Dodds, Michael
AU - Dittmayer, Carsten
AU - Moss, Jon
AU - Rose, Jamie
AU - Szymkowiak, Stefan
AU - Amann, Lukas
AU - McColl, Barry W
AU - Prinz, Marco
AU - Spires-Jones, Tara
AU - Stenzel, Werner
AU - Horsburgh, Karen
AU - Hendriks, Jerome J A
AU - Pridans, Clare
AU - Muramatsu, Rieko
AU - Williams, Anna C
AU - Priller, Josef
AU - Miron, Véronique E
PY - 2023/1/5
Y1 - 2023/1/5
N2 - 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.
AB - 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.
U2 - 10.1038/s41586-022-05534-y
DO - 10.1038/s41586-022-05534-y
M3 - Article
VL - 613
SP - 120
EP - 129
JO - Nature
JF - Nature
SN - 0028-0836
ER -