ArticleProceedings of the National Academy of Sciences of the United States of America2020
Microglia depletion exacerbates demyelination and impairs remyelination in a neurotropic coronavirus infection.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 87 citations in OpenAlex.
- IgA Deficiency Exacerbates an Animal Model of Multiple Sclerosis Induced with Theiler's Virus.Cells · 2026Article
- CSF1R inhibition following antibody mediated demyelination has limited impact on remyelination.Acta neuropathologica communications · 2026Article
- Neuregulin-1 facilitates myelin regeneration through microglia-mediated mechanisms in a mouse model of chronic demyelination.Nature communications · 2026Article
- Microglial-Derived IGF-1 Serves as a Regulator for Neuroimmune Homeostasis During Viral-Induced Demyelination.Viruses · 2026Article
- Prior murine neurotropic coronavirus infection ameliorates experimental autoimmune encephalitis.Journal of autoimmunity · 2026Article
- Heterologous expression of HCoV-HKU1 ORF 7b by mouse hepatitis virus protects against severe disease during murine infection.PLoS pathogens · 2025Article
- Unraveling the complexities of neurotropic virus infection and immune evasion.Microbiology and molecular biology reviews : MMBR · 2025Review
- Inosine Treatment Attenuates White Matter Injury in Neonatal Rats Exposed to Maternal Inflammation.Neurochemical research · 2025Article
- Article
- Microglia dysfunction, neurovascular inflammation and focal neuropathologies are linked to IL-1- and IL-6-related systemic inflammation in COVID-19.Nature neuroscience · 2025Article
- Long-term reprogramming of primed microglia after moderate inhibition of CSF1R signaling.Glia · 2025Article
- Demyelination and Remyelination: General Principles.Advances in neurobiology · 2025Review
- Distinct olfactory mucosal macrophage populations mediate neuronal maintenance and pathogen defense.Mucosal immunology · 2024Article
- Bruton's tyrosine kinase inhibition ameliorated neuroinflammation during chronic white matter ischemia.Journal of neuroinflammation · 2024Article
- Multiple sclerosis: the NLRP3 inflammasome, gasdermin D, and therapeutics.Annals of translational medicine · 2024Review
- Electrical stimulation of the vagus nerve ameliorates inflammation and disease activity in a rat EAE model of multiple sclerosis.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Cystatin F attenuates neuroinflammation and demyelination following murine coronavirus infection of the central nervous system.Journal of neuroinflammation · 2024Article
- The Emerging Role of Microglial Hv1 as a Target for Immunomodulation in Myelin Repair.Aging and disease · 2024Review
- Review
- Microglia as potential key regulators in viral-induced neuroinflammation.Frontiers in cellular neuroscience · 2024Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.