The pathogenesis of prion diseases, a class of transmissible fatal neurodegenerative diseases in humans and animals, is still unclear. The aim of this study was to identify the differentially regulated genes that correlate with the development of prion diseases for a better understanding of their pathological mechanisms. We employed Affymetrix Mouse Expression Arrays 430A containing >22,000 transcripts and compared the global gene expression profiles from brains of mice who were intracerebrally inoculated with scrapie strains ME7 and RML with those from brains of uninfected and mock-infected mice. The microarray data were analyzed by Significance Analysis of Microarrays, revealing 121 genes whose expression increased at least twofold in both ME7-and RML-infected mouse brains, with an estimated false discovery rate of <5%. These genes encode proteins involved in proteolysis, protease inhibition, cell growth and maintenance, the immune response, signal transduction, cell adhesion, and molecular metabolism. The time course of expression generally showed up-regulation of these genes from 120 days postinoculation (dpi) for ME7-inoculated mouse brains and from 90 dpi for RML-inoculated mouse brains. The onset of elevated expression correlated temporally with the onset of PrP Sc accumulation and the activation of glia, which may have contributed to neuronal cell death. Among the differentially regulated genes reported in the present study, the emergence of genes for several cathepsins and S100 calcium binding proteins was conspicuous. These and other genes reported here may represent novel potential diagnostic and therapeutic targets for prion disease.

Dermal papilla cells (DPC) and dermal fibroblasts (DFB) derived from hair follicles from two different body sites (head, flank) of four male, castrated beagle dogs were incubated for 24 h with radioactive progesterone (P4). Thin-layer chromatography was used for separation and autoradiography for identification of the radioactive metabolites. In DFB the main metabolites were cortisol and 4-pregnene-11beta-ol-3,20-dione, whereas in DPC they were 5alpha-pregnane-3,20-dione and cortisol. The highest percentage of metabolism of P4 was found in DFB of the head. Smaller amounts of other metabolites were found in both cell types of both locations.

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