2. Academic Validation
  3. Microglia regulate central nervous system myelin growth and integrity

Microglia regulate central nervous system myelin growth and integrity

  • Nature. 2022 Dec 14. doi: 10.1038/s41586-022-05534-y.
Niamh B McNamara 1 2 3,  David A D Munro 1 4,  Nadine Bestard-Cuche 5,  Akiko Uyeda 6,  Jeroen F J Bogie 7 8,  Alana Hoffmann 1 2 3,  Rebecca K Holloway 1 2 3 9 10 11,  Irene Molina-Gonzalez 1 2 3,  Katharine E Askew 2,  Stephen Mitchell 12,  William Mungall 13,  Michael Dodds 13,  Carsten Dittmayer 14,  Jonathan Moss 5,  Jamie Rose 1 2,  Stefan Szymkowiak 1 2,  Lukas Amann 15 16,  Barry W McColl 1 2,  Marco Prinz 15 16,  Tara L Spires-Jones 1 2,  Werner Stenzel 14,  Karen Horsburgh 2,  Jerome J A Hendriks 7 8,  Clare Pridans 17 18 19,  Rieko Muramatsu 6,  Anna Williams 1 5,  Josef Priller # 1 4 20 21,  Veronique E Miron # 22 23 24 25 26 27
Affiliations

Affiliations

  • 1 UK Dementia Research Institute at The University of Edinburgh, Edinburgh, UK.
  • 2 Centre for Discovery Brain Sciences, Chancellor's Building, The University of Edinburgh, Edinburgh, UK.
  • 3 Medical Research Council Centre for Reproductive Health, The Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, UK.
  • 4 Centre for Clinical Brain Sciences, Chancellor's Building, The University of Edinburgh, Edinburgh, UK.
  • 5 Centre for Regenerative Medicine, Institute for Regeneration and Repair, The University of Edinburgh, Edinburgh, UK.
  • 6 Departments of Molecular Pharmacology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Japan.
  • 7 Department of Immunology and Infection, Biomedical Research Institute, Hasselt University, Hasselt, Belgium.
  • 8 University MS Centre, Hasselt University, Hasselt, Belgium.
  • 9 Barlo Multiple Sclerosis Centre, St Michael's Hospital, Toronto, Ontario, Canada.
  • 10 Keenan Research Centre for Biomedical Science, St Michael's Hospital, Toronto, Ontario, Canada.
  • 11 Department of Immunology, The University of Toronto, Toronto, Ontario, Canada.
  • 12 Wellcome Trust Centre for Cell Biology, King's Buildings, The University of Edinburgh, Edinburgh, UK.
  • 13 Biological and Veterinary Services, Chancellor's Building, The University of Edinburgh, Edinburgh, UK.
  • 14 Department of Neuropathology and Neurocure Clinical Research Center, Charité-Universitätsmedizin Berlin, Berlin, Germany.
  • 15 Institute of Neuropathology, Centre for Basics in NeuroModulation, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • 16 Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany.
  • 17 Centre for Inflammation Research, The Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, UK.
  • 18 Simons Initiative for the Developing Brain, Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, UK.
  • 19 Muir Maxwell Epilepsy Centre, University of Edinburgh, Edinburgh, UK.
  • 20 Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany.
  • 21 Neuropsychiatry and Laboratory of Molecular Psychiatry, Charité-Universitätsmedizin Berlin and DZNE, Berlin, Germany.
  • 22 UK Dementia Research Institute at The University of Edinburgh, Edinburgh, UK. Veronique.Miron@unityhealth.to.
  • 23 Centre for Discovery Brain Sciences, Chancellor's Building, The University of Edinburgh, Edinburgh, UK. Veronique.Miron@unityhealth.to.
  • 24 Medical Research Council Centre for Reproductive Health, The Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, UK. Veronique.Miron@unityhealth.to.
  • 25 Barlo Multiple Sclerosis Centre, St Michael's Hospital, Toronto, Ontario, Canada. Veronique.Miron@unityhealth.to.
  • 26 Keenan Research Centre for Biomedical Science, St Michael's Hospital, Toronto, Ontario, Canada. Veronique.Miron@unityhealth.to.
  • 27 Department of Immunology, The University of Toronto, Toronto, Ontario, Canada. Veronique.Miron@unityhealth.to.
  • # Contributed equally.
PMID: 36517604 DOI: 10.1038/s41586-022-05534-y
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.

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