Campus Units

Veterinary Pathology, Biomedical Sciences, Statistics

Document Type

Article

Publication Version

Published Version

Publication Date

1-1-2020

Journal or Book Title

Veterinary Pathology

Volume

57

Issue

1

First Page

90

Last Page

107

DOI

10.1177%2F0300985819861708

Abstract

Mammalian transmissible spongiform encephalopathies (TSEs) display marked activation of astrocytes and microglia that precedes neuronal loss. Investigation of clinical parallels between TSEs and other neurodegenerative protein misfolding diseases, such as Alzheimer’s disease, has revealed similar patterns of neuroinflammatory responses to the accumulation of self-propagating amyloids. The contribution of glial activation to the progression of protein misfolding diseases is incompletely understood, with evidence for mediation of both protective and deleterious effects. Glial populations are heterogeneously distributed throughout the brain and capable of dynamic transitions along a spectrum of functional activation states between pro- and antiinflammatory polarization extremes. Using a murine model of Rocky Mountain Laboratory scrapie, the neuroinflammatory response to prion infection was characterized by evaluating glial activation across 15 brain regions over time and correlating it to traditional markers of prion neuropathology, including vacuolation and PrPSc deposition. Quantitative immunohistochemistry was used to evaluate glial expression of iNOS and Arg1, markers of classical and alternative glial activation, respectively. The results indicate progressive upregulation of iNOS in microglia and a mixed astrocytic profile featuring iNOS expression in white matter tracts and detection of Arg1-positive populations throughout the brain. These data establish a temporospatial lesion profile for this prion infection model and demonstrate evidence of multiple glial activation states.

Comments

This article is published as Michael, Alyona V., Justin J. Greenlee, Tyler A. Harm, S. Jo Moore, Min Zhang, Melissa S. Lind, M. Heather West Greenlee, and Jodi D. Smith. "In Situ Temporospatial Characterization of the Glial Response to Prion Infection." Veterinary Pathology 57, no. 1 (2020): 90-107. DOI: 10.1177%2F0300985819861708.

Rights

Works produced by employees of the U.S. Government as part of their official duties are not copyrighted within the U.S. The content of this document is not copyrighted.

Language

en

File Format

application/pdf

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