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>