Microglia Are Critical in Host Defense against Prion Disease
Open accessAbstract
Microglia contribute to many aspects of health and disease. When activated, microglia can be beneficial by repairing damage in the central nervous system (CNS) or they can turn harmful by becoming neurotoxic. In prion and prionlike diseases, the involvement of microglia in disease is unclear. Previous studies suggest that microglia can either speed up or slow down disease. In this study, we infected mice with prions and depleted microglia from the brains of mice using PLX5622, an effective CSF-1R tyrosine kinase inhibitor. Microglia were markedly reduced in brains, and prion disease was accelerated, so that mice needed to be euthanized 20 to 33 days earlier than infected control mice due to advanced clinical disease. Similar results occurred when mice were treated with PLX5622 at 80 days after infection, which was just prior to the start of clinical signs. Thus, microglia are important for removing prions, and the disease is faster when microglia are depleted.
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Partial depletion of microglia in early stages of the disease enhances the accumulation of prions in the brain and accelerates the onset of clinical disease.
“Moreover, partial depletion of microglia in early stages of the disease was reported to enhance the accumulation of prions in the brain and accelerate the onset of clinical disease [46].”
From Loss of Homeostatic Microglia Signature in Prion Diseases (2022) · cites this paper as [46]
The number of activated microglia is highest in the thalamus, a region where reactive microglia can already be detected at a preclinical time point.
“The number of activated microglia is highest in the thalamus, a region where reactive microglia can already be detected at a preclinical time point (see Figure 2) [45,46,47].”
From Loss of Homeostatic Microglia Signature in Prion Diseases (2022) · cites this paper as [46]
In terminal prion disease, microglia morphology changes from the ramified presentation typical in homeostasis to a bushy/reactive or even amoeboid morphology in a region-dependent manner.
“First, microglia morphology is changed from the ramified presentation typical in homeostasis to a bushy/reactive or even amoeboid morphology in a region-dependent manner (Figure 3A,B) [45,46,47].”
From Loss of Homeostatic Microglia Signature in Prion Diseases (2022) · cites this paper as [46]
The region-specific increase in microglia numbers during the course of prion disease has been shown with several mouse-adapted prion strains and may be aggravated by systemic infection.
“The region-specific increase in microglia numbers during the course of a prion disease had already been shown with several mouse adapted prion strains [45,46,47] and may be aggravated by systemic infection [48,49].”
From Loss of Homeostatic Microglia Signature in Prion Diseases (2022) · cites this paper as [46]
The appearance of reactive microglia starts before the onset of symptoms, can be detected at around day 70-80 in a region-dependent manner, and is visible mainly in the thalamus at this time point.
“Different groups have independently shown that the appearance of reactive microglia starts before the onset of symptoms, can be detected at around day 70–80 in a region-dependent manner, and is visible mainly in the thalamus at this time point (Figure 2) [45,46,47].”
From Loss of Homeostatic Microglia Signature in Prion Diseases (2022) · cites this paper as [46]
Although microglia numbers are significantly increased in all four brain regions at the terminal stage, the increase is highest in the thalamus.
“Although microglia numbers were significantly increased in all four brain regions at the terminal stage, the increase was highest in the thalamus [45,46,47].”
From Loss of Homeostatic Microglia Signature in Prion Diseases (2022) · cites this paper as [46]
Several proinflammatory cytokines, including TNF α, IL 1α, and C1qa, are upregulated in the brain during the prion disease course.
“Several proinflammatory cytokines are upregulated in the brain during the prion disease course including TNF α, IL 1α, and C1qa [46,69,70,71,72,73].”
From Loss of Homeostatic Microglia Signature in Prion Diseases (2022) · cites this paper as [46]
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References 48 · Cited by 94
- Authors
- Carroll, J. A., Race, B., Williams, K., Striebel, J., & Chesebro, B.
- Affiliations
- National Institutes of Health (US)
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2018-08
- Volume
- 92
- Issue
- 15
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- PMC
- PMC6052316
- OpenAlex
- W2804748500
- Cited by
- 94
- References
- 48
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 13 · 2023: 7 · 2022: 15 · 2021: 15 · 2020: 17 · 2019: 13 · 2018: 4
- FWCI
- 4.36
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Virology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- HHS | NIH | National Institute of Allergy and Infectious Diseases (Intramural Research Program of the NIH)
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Intramural Research Program of the NIH)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- microglia, prion disease, prion clearance, microglial depletion, PLX5622, CSF1R inhibitor, neuroinflammation, host defense, mouse model
- MeSH terms
- Administration, Oral, Animals, Disease Models, Animal, Female, Male, Organic Chemicals, Scrapie, Severity of Illness Index, Receptors, Granulocyte-Macrophage Colony-Stimulating Factor, Apoptosis, Microglia, PrPSc Proteins, Mice
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