10.1371/journal.ppat.1005551 James A. Carroll James A. Carroll James F. Striebel James F. Striebel Alejandra Rangel Alejandra Rangel Tyson Woods Tyson Woods Katie Phillips Katie Phillips Karin E. Peterson Karin E. Peterson Brent Race Brent Race Bruce Chesebro Bruce Chesebro Prion Strain Differences in Accumulation of PrPSc on Neurons and Glia Are Associated with Similar Expression Profiles of Neuroinflammatory Genes: Comparison of Three Prion Strains Public Library of Science 2016 polytropic Friend retrovirus Strain 22 L upregulated genes misfolded protein increases Prion Strains Misfolding prion diseases mouse scrapie strains Similar Expression Profiles host prion protein Prion Strain Differences RML cell specificity PrPSc accumulation CNS 2016-04-05 03:30:01 Dataset https://plos.figshare.com/articles/dataset/Prion_Strain_Differences_in_Accumulation_of_PrPSc_on_Neurons_and_Glia_Are_Associated_with_Similar_Expression_Profiles_of_Neuroinflammatory_Genes_Comparison_of_Three_Prion_Strains/3156625 <div><p>Misfolding and aggregation of host proteins are important features of the pathogenesis of neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia and prion diseases. In all these diseases, the misfolded protein increases in amount by a mechanism involving seeded polymerization. In prion diseases, host prion protein is misfolded to form a pathogenic protease-resistant form, PrPSc, which accumulates in neurons, astroglia and microglia in the CNS. Here using dual-staining immunohistochemistry, we compared the cell specificity of PrPSc accumulation at early preclinical times post-infection using three mouse scrapie strains that differ in brain regional pathology. PrPSc from each strain had a different pattern of cell specificity. Strain 22L was mainly associated with astroglia, whereas strain ME7 was mainly associated with neurons and neuropil. In thalamus and cortex, strain RML was similar to 22L, but in substantia nigra, RML was similar to ME7. Expression of 90 genes involved in neuroinflammation was studied quantitatively using mRNA from thalamus at preclinical times. Surprisingly, despite the cellular differences in PrPSc accumulation, the pattern of upregulated genes was similar for all three strains, and the small differences observed correlated with variations in the early disease tempo. Gene upregulation correlated with activation of both astroglia and microglia detected in early disease prior to vacuolar pathology or clinical signs. Interestingly, the profile of upregulated genes in scrapie differed markedly from that seen in two acute viral CNS diseases (LaCrosse virus and BE polytropic Friend retrovirus) that had reactive gliosis at levels similar to our prion-infected mice.</p></div>