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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Virus and Prion Research » Research » Publications at this Location » Publication #330776

Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES

Location: Virus and Prion Research

Title: Temporospatial distribution of microglial activation in a murine model of scrapie

Author
item MICHAEL, A - Iowa State University
item HARM, T - Iowa State University
item Greenlee, Justin
item WEST GREENLEE, M - Iowa State University
item SMITH, J - Iowa State University

Submitted to: American College of Veterinary Pathologists Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 10/6/2016
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: Mouse models of prion disease offer the advantages of genetic homogeneity and short incubation times while retaining the disease phenotype of natural mammalian hosts. Intracranial (IC) inoculation of C57BL/6 mice with a mouse-adapted scrapie strain (RML) yields uniform incubation periods with a rapid manifestation of histopathologic changes including spongiform change, abnormal PrP accumulation, and astrogliosis. The current study aimed to further characterize neuropathologic markers of prion disease by examining temporospatial patterns of microglial activation. Weaned C57BL/6 mice were inoculated with RML brain homogenate and killed at 30-day intervals until the onset of clinical signs at 155 days post-inoculation. Immunoreactivity of ionized calcium-binding adapter molecule 1 (Iba1), a cytoplasmic microglial protein upregulated in response to neuroinflammation, was quantified across 17 brain regions within 6 standard transverse sections and compared to mock-inoculated controls. Iba-1 immunoreactivity demonstrated an increased number of microglia and a transition from resting (ramified) to active (phagocytic) morphology at 90 days post-infection that progressively increased through the terminal stages of disease. The microglial response to infection was most robust in the midbrain and thalamus, correlating to previously reported patterns of astrocyte activation in this model. Systematic characterization of microgliosis in this model suggests a role for microglial activation early in disease progression.