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

Cell Reports (Dec 2023)

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

Journal volume & issue: Vol. 42, no. 12
p. 113574

Abstract

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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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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