Microglia regulate central nervous system myelin growth and integrity

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 and Veronique E. Miron ()
Additional contact information
Niamh B. McNamara: UK Dementia Research Institute at The University of Edinburgh
David A. D. Munro: UK Dementia Research Institute at The University of Edinburgh
Nadine Bestard-Cuche: The University of Edinburgh
Akiko Uyeda: National Center of Neurology and Psychiatry
Jeroen F. J. Bogie: Hasselt University
Alana Hoffmann: UK Dementia Research Institute at The University of Edinburgh
Rebecca K. Holloway: UK Dementia Research Institute at The University of Edinburgh
Irene Molina-Gonzalez: UK Dementia Research Institute at The University of Edinburgh
Katharine E. Askew: The University of Edinburgh
Stephen Mitchell: The University of Edinburgh
William Mungall: The University of Edinburgh
Michael Dodds: The University of Edinburgh
Carsten Dittmayer: Charité-Universitätsmedizin Berlin
Jonathan Moss: The University of Edinburgh
Jamie Rose: UK Dementia Research Institute at The University of Edinburgh
Stefan Szymkowiak: UK Dementia Research Institute at The University of Edinburgh
Lukas Amann: University of Freiburg
Barry W. McColl: UK Dementia Research Institute at The University of Edinburgh
Marco Prinz: University of Freiburg
Tara L. Spires-Jones: UK Dementia Research Institute at The University of Edinburgh
Werner Stenzel: Charité-Universitätsmedizin Berlin
Karen Horsburgh: The University of Edinburgh
Jerome J. A. Hendriks: Hasselt University
Clare Pridans: The University of Edinburgh
Rieko Muramatsu: National Center of Neurology and Psychiatry
Anna Williams: UK Dementia Research Institute at The University of Edinburgh
Josef Priller: UK Dementia Research Institute at The University of Edinburgh
Veronique E. Miron: UK Dementia Research Institute at The University of Edinburgh

Nature, 2023, vol. 613, issue 7942, 120-129

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41586-022-05534-y

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