Microglia deficiency accelerates prion disease but does not enhance prion accumulation in the brain. Issue 11 (19th July 2022)

• Record Type: Journal Article
• Authors: Bradford, Barry M.; McGuire, Lynne I.; Hume, David A.; Pridans, Clare; Mabbott, Neil A.
• Is Part Of: Glia. Volume 70:Issue 11(2022)
• Page Start: 2169
• Page End: 2187
• Publication Date: 2022-07-19
• Subjects: central nervous system -- microglia -- neurodegeneration -- prion disease -- reactive astrocyte; Neuroglia -- Periodicals; Neurology -- Periodicals; 611.0188
• DOI: 10.1002/glia.24244
• Languages: English
• ISSNs: 0894-1491

Abstract

Abstract: Prion diseases are transmissible, neurodegenerative disorders associated with misfolding of the prion protein. Previous studies show that reduction of microglia accelerates central nervous system (CNS) prion disease and increases the accumulation of prions in the brain, suggesting that microglia provide neuroprotection by phagocytosing and destroying prions. In Csf1r ΔFIRE mice, the deletion of an enhancer within Csf1r specifically blocks microglia development, however, their brains develop normally and show none of the deficits reported in other microglia‐deficient models. Csf1r ΔFIRE mice were used as a refined model in which to study the impact of microglia‐deficiency on CNS prion disease. Although Csf1r ΔFIRE mice succumbed to CNS prion disease much earlier than wild‐type mice, the accumulation of prions in their brains was reduced. Instead, astrocytes displayed earlier, non‐polarized reactive activation with enhanced phagocytosis of neuronal contents and unfolded protein responses. Our data suggest that rather than simply phagocytosing and destroying prions, the microglia instead provide host‐protection during CNS prion disease and restrict the harmful activities of reactive astrocytes. Main Points: CNS prion disease is accelerated in mice completely lacking microglia. The rate of prion accumulation in the brain was unaltered in absence of microglia. Microglia provide host‐protection during CNS prion disease independent of prion clearance.