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Microglia depletion exacerbates demyelination and impairs remyelination in a neurotropic coronavirus infection.

ABSTRACT: Microglia are considered both pathogenic and protective during recovery from demyelination, but their precise role remains ill defined. Here, using an inhibitor of colony stimulating factor 1 receptor (CSF1R), PLX5622, and mice infected with a neurotropic coronavirus (mouse hepatitis virus [MHV], strain JHMV), we show that depletion of microglia during the time of JHMV clearance resulted in impaired myelin repair and prolonged clinical disease without affecting the kinetics of virus clearance. Microglia were required only during the early stages of remyelination. Notably, large deposits of extracellular vesiculated myelin and cellular debris were detected in the spinal cords of PLX5622-treated and not control mice, which correlated with decreased numbers of oligodendrocytes in demyelinating lesions in drug-treated mice. Furthermore, gene expression analyses demonstrated differential expression of genes involved in myelin debris clearance, lipid and cholesterol recycling, and promotion of oligodendrocyte function. The results also demonstrate that microglial functions affected by depletion could not be compensated by infiltrating macrophages. Together, these results demonstrate that microglia play key roles in debris clearance and in the initiation of remyelination following infection with a neurotropic coronavirus but are not necessary during later stages of remyelination.

SUBMITTER: Sariol A

PROVIDER: S-EPMC7533697 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Microglia depletion exacerbates demyelination and impairs remyelination in a neurotropic coronavirus infection.

Sariol Alan A Mackin Samantha S Allred Merri-Grace MG Ma Chen C Zhou Yu Y Zhang Qinran Q Zou Xiufen X Abrahante Juan E JE Meyerholz David K DK Perlman Stanley S

Proceedings of the National Academy of Sciences of the United States of America 20200914 39

Microglia are considered both pathogenic and protective during recovery from demyelination, but their precise role remains ill defined. Here, using an inhibitor of colony stimulating factor 1 receptor (CSF1R), PLX5622, and mice infected with a neurotropic coronavirus (mouse hepatitis virus [MHV], strain JHMV), we show that depletion of microglia during the time of JHMV clearance resulted in impaired myelin repair and prolonged clinical disease without affecting the kinetics of virus clearance. M ...[more]

PMID: 32929007

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Dataset Information

Microglia depletion exacerbates demyelination and impairs remyelination in a neurotropic coronavirus infection.

Publications

Microglia depletion exacerbates demyelination and impairs remyelination in a neurotropic coronavirus infection.

Similar Datasets

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