Microglia promote remyelination independent of their role in clearing myelin debris
Charbel S. Baaklini,
Madelene F.S. Ho,
Tristan Lange,
Brady P. Hammond,
Sharmistha P. Panda,
Martin Zirngibl,
Sameera Zia,
Kassandre Himmelsbach,
Heli Rana,
Braxton Phillips,
Daria Antoszko,
Jeremies Ibanga,
Mizuki Lopez,
Kelly V. Lee,
Michael B. Keough,
Andrew V. Caprariello,
Bradley J. Kerr,
Jason R. Plemel
Affiliations
Charbel S. Baaklini
Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2R3, Canada
Madelene F.S. Ho
Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2R3, Canada
Tristan Lange
Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2R3, Canada
Brady P. Hammond
Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2R3, Canada
Sharmistha P. Panda
Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2R3, Canada
Martin Zirngibl
Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2R3, Canada
Sameera Zia
Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2R3, Canada
Kassandre Himmelsbach
Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2R3, Canada
Heli Rana
Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2R3, Canada
Braxton Phillips
Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2R3, Canada
Daria Antoszko
Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2R3, Canada
Jeremies Ibanga
Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2R3, Canada
Mizuki Lopez
Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2R3, Canada
Kelly V. Lee
Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2R3, Canada
Michael B. Keough
Division of Neurosurgery, Department of Surgery, University of Alberta, Edmonton, AB T6G 2R3, Canada
Andrew V. Caprariello
Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Cumming School of Medicine, Calgary, AB T2N 1N4, Canada
Bradley J. Kerr
Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2R3, Canada; Department of Anesthesiology & Pain Medicine, University of Alberta, Edmonton, AB T6G 2R3, Canada
Jason R. Plemel
Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2R3, Canada; Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB T6G 2R3, Canada; Department of Medicine, Division of Neurology, University of Alberta, Edmonton, AB T6G 2R3, Canada; Corresponding author
Summary: Multiple sclerosis (MS) is an inflammatory disease characterized by myelin loss. While therapies exist to slow MS progression, no treatment currently exists for remyelination. Remyelination, linked to reduced disability in MS, relies on microglia and monocyte-derived macrophages (MDMs). This study aims to understand the role of microglia during remyelination by lineage tracing and depleting them. Microglial lineage tracing reveals that both microglia and MDMs initially accumulate, but microglia later dominate the lesion. Microglia and MDMs engulf equal amounts of inhibitory myelin debris, but after microglial depletion, MDMs compensate by engulfing more myelin debris. Microglial depletion does, however, reduce the recruitment and proliferation of oligodendrocyte progenitor cells (OPCs) and impairs their subsequent differentiation and remyelination. These findings underscore the essential role of microglia during remyelination and offer insights for enhancing this process by understanding microglial regulation of remyelination.
