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Updated: Jun 22, 2026
Adipose-Derived Mesenchymal Stromal Cells Co-Cultured with Primary Mixed Glia to Reduce Prion-Induced Inflammation
Published on: August 11, 2023
Limited transcriptional response of ovine microglia to prion accumulation
James B Stanton1, Donald P Knowles, Douglas R Call
1Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164-7040, USA. jstanton@vetmed.wsu.edu
Abstract:
The conversion of normal cellular prion protein to disease-associated prion protein (PrP(Sc)) is a fundamental component of prion disease pathogenesis. The molecular mechanisms contributing to prion conversion and the impact of PrP(Sc) accumulation on cellular biology are not fully understood. To further define the molecular changes associated with PrP(Sc) accumulation in cultured cells, the transcriptional profile of PrP(Sc)-accumulating primary ovine microglia was compared to the profile of PrP(Sc)-lacking microglia using the Affymetrix Bovine Genome Array. The experimental design included three biological replicates, each with three technical replicates, and samples that were collected at the point of near maximal PrP(Sc) accumulation levels as measured by ELISA. The array analysis revealed only 19 upregulated genes and 30 downregulated genes in PrP(Sc)-accumulating microglia. The results support the hypothesis that chronic PrP(Sc) accumulation in cultured microglia results in a limited transcriptional response.
Insights
Prion disease pathogenesis involves prion protein conversion. Chronic accumulation of disease-associated prion protein (PrPSc) in ovine microglia triggers a limited transcriptional response, suggesting minimal cellular adaptation.
Area of Science:
- Neuroscience
- Molecular Biology
- Immunology
Background:
- Prion diseases are linked to the conversion of normal cellular prion protein (PrPC) to disease-associated prion protein (PrPSc).
- The molecular mechanisms and cellular impacts of PrPSc accumulation remain incompletely understood.
- Microglia play a crucial role in neuroinflammation and prion disease pathogenesis.
Purpose of the Study:
- To investigate the transcriptional changes in primary ovine microglia upon accumulation of PrPSc.
- To understand the cellular response to chronic prion protein conversion in microglia.
Main Methods:
- Primary ovine microglia cultures were established and exposed to PrPSc.
- Gene expression profiling was performed using the Affymetrix Bovine Genome Array.
- Enzyme-linked immunosorbent assay (ELISA) was used to quantify PrPSc accumulation levels.
Main Results:
- A limited number of genes showed differential expression in PrPSc-accumulating microglia compared to control microglia.
- Only 19 genes were upregulated and 30 genes were downregulated.
- This indicates a restricted transcriptional response to chronic PrPSc accumulation.
Conclusions:
- Chronic accumulation of PrPSc in cultured microglia elicits a minimal transcriptional response.
- The findings suggest that microglia may have a limited capacity to adapt to prion protein misfolding at the transcriptional level.
- Further research is needed to explore other cellular mechanisms involved in prion disease pathogenesis in microglia.
