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

doi:10.1016/j.celrep.2023.113574

Microglia promote remyelination independent of their role in clearing myelin debris

Cell Rep. 2023 Dec 26;42(12):113574. doi: 10.1016/j.celrep.2023.113574. Epub 2023 Dec 14.

Authors

Charbel S Baaklini¹, Madelene F S Ho¹, Tristan Lange¹, Brady P Hammond¹, Sharmistha P Panda¹, Martin Zirngibl¹, Sameera Zia¹, Kassandre Himmelsbach¹, Heli Rana¹, Braxton Phillips¹, Daria Antoszko¹, Jeremies Ibanga¹, Mizuki Lopez¹, Kelly V Lee¹, Michael B Keough², Andrew V Caprariello³, Bradley J Kerr⁴, Jason R Plemel⁵

Affiliations

¹ Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2R3, Canada.
² Division of Neurosurgery, Department of Surgery, University of Alberta, Edmonton, AB T6G 2R3, Canada.
³ Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Cumming School of Medicine, Calgary, AB T2N 1N4, Canada.
⁴ 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.
⁵ 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. Electronic address: jrplemel@ualberta.ca.

PMID: 38100356
DOI: 10.1016/j.celrep.2023.113574

Abstract

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.

Keywords: CP: Immunology; CP: Neuroscience; differentiation; lysophosphatidylcholine; microglia; monocyte-derived macrophages; myelin debris; oligodendrocyte; oligodendrocyte progenitor cell; phagocytosis; proliferation; remyelination.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Demyelinating Diseases* / pathology
Humans
Macrophages / pathology
Microglia / pathology
Multiple Sclerosis* / pathology
Myelin Sheath / pathology
Remyelination*