Limited transcriptional response of ovine microglia to prion accumulation

The conversion of normal cellular prion protein to disease-associated prion protein (PrPSc) is a fundamental component of prion disease pathogenesis. The molecular mechanisms contributing to prion conversion and the impact of PrPSc accumulation on cellular biology are not fully understood. To further define the molecular changes associated with PrPSc accumulation in cultured cells, the transcriptional profile of PrPSc-accumulating primary ovine microglia was compared to the profile of PrPSc-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 PrPSc accumulation levels as measured by ELISA. The array analysis revealed only 19 upregulated genes and 30 downregulated genes in PrPSc-accumulating microglia. The results support the hypothesis that chronic PrPSc accumulation in cultured microglia results in a limited transcriptional response.