Microglia Are Critical in Host Defense against Prion Disease

Journal of Virology
James A CarrollBruce Chesebro

Abstract

Microglial cells in the central nervous system play important roles in neurodevelopment and resistance to infection, yet microglia can become neurotoxic under some conditions. An early event during prion infection is the activation of microglia and astrocytes in the brain prior to damage or death of neurons. Previous prion disease studies using two different strategies to manipulate signaling through the microglial receptor CSF-1R reported contrary effects on survival from prion disease. However, in these studies, reductions of microglial numbers and function were variable, thus confounding interpretation of the results. In the present work, we used oral treatment with a potent inhibitor of CSF-1R, PLX5622, to eliminate 78 to 90% of microglia from cortex early during the course of prion infection. Oral drug treatment early after infection with the RML scrapie strain significantly accelerated vacuolation, astrogliosis, and deposition of disease-associated prion protein. Furthermore, drug-treated mice had advanced clinical disease requiring euthanasia 31 days earlier than untreated control mice. Similarly, PLX5622 treatment during the preclinical phase at 80 days postinfection with RML scrapie also accelerated disease and resulte...Continue Reading

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Citations

Jan 1, 2019·PloS One·James A CarrollBruce Chesebro
Mar 26, 2019·PLoS Pathogens·Cassandra M BurkeSurachai Supattapone
Aug 20, 2019·Molecular Neurodegeneration·Sonia GeorgePatrik Brundin
Mar 27, 2019·Acta Neuropathologica Communications·James F StriebelBruce Chesebro
Aug 19, 2020·International Journal of Molecular Sciences·Isabel M GuijarroMarta Monzón
May 7, 2020·International Journal of Molecular Sciences·Isabel M GuijarroMarta Monzón
Jan 18, 2019·Viruses·James A Carroll, Bruce Chesebro
Jun 2, 2020·Journal of Neuroinflammation·Elisabeth G VichayaRobert Dantzer
Jun 15, 2019·Acta Neuropathologica Communications·Bradley R GrovemanCathryn L Haigh
Nov 11, 2018·Journal of Neuroinflammation·Rachel E BennettBradley T Hyman
Oct 8, 2020·International Journal of Molecular Sciences·Neil A MabbottDavid S Donaldson
Oct 24, 2020·International Journal of Molecular Sciences·Caterina PeggionMaria Lina Massimino
Mar 7, 2021·International Journal of Molecular Sciences·Bei LiCaihong Zhu
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Sep 28, 2021·Acta Neuropathologica Communications·Joanna E PankiewiczMartin J Sadowski
Dec 7, 2021·Frontiers in Aging Neuroscience·Banglian HuHonghua Zheng

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