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Microglia regulate central nervous system myelin growth and integrity

Author

Listed:
  • Niamh B. McNamara

    (UK Dementia Research Institute at The University of Edinburgh
    The University of Edinburgh
    The University of Edinburgh)

  • David A. D. Munro

    (UK Dementia Research Institute at The University of Edinburgh
    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
    University MS Centre, Hasselt University)

  • Alana Hoffmann

    (UK Dementia Research Institute at The University of Edinburgh
    The University of Edinburgh
    The University of Edinburgh)

  • Rebecca K. Holloway

    (UK Dementia Research Institute at The University of Edinburgh
    The University of Edinburgh
    The University of Edinburgh
    St Michael’s Hospital)

  • Irene Molina-Gonzalez

    (UK Dementia Research Institute at The University of Edinburgh
    The University of Edinburgh
    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
    The University of Edinburgh)

  • Stefan Szymkowiak

    (UK Dementia Research Institute at The University of Edinburgh
    The University of Edinburgh)

  • Lukas Amann

    (University of Freiburg
    University of Freiburg)

  • Barry W. McColl

    (UK Dementia Research Institute at The University of Edinburgh
    The University of Edinburgh)

  • Marco Prinz

    (University of Freiburg
    University of Freiburg)

  • Tara L. Spires-Jones

    (UK Dementia Research Institute at The University of Edinburgh
    The University of Edinburgh)

  • Werner Stenzel

    (Charité-Universitätsmedizin Berlin)

  • Karen Horsburgh

    (The University of Edinburgh)

  • Jerome J. A. Hendriks

    (Hasselt University
    University MS Centre, Hasselt University)

  • Clare Pridans

    (The University of Edinburgh
    University of Edinburgh
    University of Edinburgh)

  • Rieko Muramatsu

    (National Center of Neurology and Psychiatry)

  • Anna Williams

    (UK Dementia Research Institute at The University of Edinburgh
    The University of Edinburgh)

  • Josef Priller

    (UK Dementia Research Institute at The University of Edinburgh
    The University of Edinburgh
    Technical University of Munich
    Charité-Universitätsmedizin Berlin and DZNE)

  • Veronique E. Miron

    (UK Dementia Research Institute at The University of Edinburgh
    The University of Edinburgh
    The University of Edinburgh
    St Michael’s Hospital)

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.

Suggested Citation

  • 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 &, 2023. "Microglia regulate central nervous system myelin growth and integrity," Nature, Nature, vol. 613(7942), pages 120-129, January.
    • Handle: RePEc:nat:nature:v:613:y:2023:i:7942:d:10.1038_s41586-022-05534-y
    DOI: 10.1038/s41586-022-05534-y
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    Cited by:

    1. Leon D. Lotter & Amin Saberi & Justine Y. Hansen & Bratislav Misic & Casey Paquola & Gareth J. Barker & Arun L. W. Bokde & Sylvane Desrivières & Herta Flor & Antoine Grigis & Hugh Garavan & Penny Gowl, 2024. "Regional patterns of human cortex development correlate with underlying neurobiology," Nature Communications, Nature, vol. 15(1), pages 1-21, December.

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