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Mice Treated Subcutaneously with Mouse LPS-Converted PrPres or LPS Alone Showed Brain Gene Expression Profiles
Dagnachew Hailemariam1, Seyed Ali Goldansaz1,2, Nathalie Daude3
1Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB T6G 2P5, Canada.
Abstract:
Previously, we showed that bacterial lipopolysaccharide (LPS) converts mouse PrPC protein to a beta-rich isoform (moPrPres) resistant to proteinase K. In this study, we aimed to test if the LPS-converted PrPres is infectious and alters the expression of genes related to prion pathology in brains of terminally sick mice. Ninety female FVB/N mice at 5 weeks of age were randomly assigned to 6 groups treated subcutaneously (sc) for 6 weeks either with: (1) Saline (CTR); (2) LPS from Escherichia coli 0111:B4 (LPS), (3) one-time sc administration of de novo generated mouse recombinant prion protein (moPrP; 29-232) rich in beta-sheet by incubation with LPS (moPrPres), (4) LPS plus one-time sc injection of moPrPres, (5) one-time sc injection of brain homogenate from Rocky Mountain Lab (RLM) scrapie strain, and (6) LPS plus one-time sc injection of RML. Results showed that all treatments altered the expression of various genes related to prion disease and neuroinflammation starting at 11 weeks post-infection and more profoundly at the terminal stage. In conclusion, sc administration of de novo generated moPrPres, LPS, and a combination of moPrPres with LPS were able to alter the expression of multiple genes typical of prion pathology and inflammation.
Insights
Bacterial lipopolysaccharide (LPS) and its converted prion protein (moPrPres) alter gene expression related to prion disease and neuroinflammation in mice. These findings suggest potential pathways in prion pathology and immune responses.
Area of Science:
- Neuroscience
- Immunology
- Biochemistry
Background:
- Bacterial lipopolysaccharide (LPS) converts mouse PrPC to a beta-rich isoform (moPrPres) resistant to proteinase K.
- The infectious nature and pathological impact of LPS-converted PrPres require further investigation.
Purpose of the Study:
- To determine if LPS-converted PrPres is infectious.
- To assess the impact of LPS-converted PrPres on prion pathology-related gene expression in mice.
Main Methods:
- Ninety mice were divided into six groups receiving saline, LPS, moPrPres, LPS plus moPrPres, RML scrapie strain, or LPS plus RML.
- Treatments were administered subcutaneously for six weeks.
- Gene expression analysis was performed at 11 weeks post-infection and at the terminal stage.
Main Results:
- All tested treatments, including LPS, moPrPres, and their combination, altered the expression of genes associated with prion disease.
- Neuroinflammation-related gene expression was also significantly affected by the treatments.
- These alterations were observed starting at 11 weeks post-infection and became more pronounced at the terminal stage.
Conclusions:
- Subcutaneous administration of de novo generated moPrPres, LPS, or a combination of both can modify gene expression patterns.
- These modifications are characteristic of prion pathology and inflammation.
- The study highlights the potential role of LPS and its converted prion protein in modulating host responses relevant to prion diseases.
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