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. 2021 Sep 21;8(9):200.
doi: 10.3390/vetsci8090200.

Mice Treated Subcutaneously with Mouse LPS-Converted PrPres or LPS Alone Showed Brain Gene Expression Profiles Characteristic of Prion Disease

Dagnachew Hailemariam  1 , Seyed Ali Goldansaz  1   2 , Nathalie Daude  3 , David S Wishart  2 , Burim N Ametaj  1
Affiliations

Mice Treated Subcutaneously with Mouse LPS-Converted PrPres or LPS Alone Showed Brain Gene Expression Profiles Characteristic of Prion Disease

Dagnachew Hailemariam et al. Vet Sci. .

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.

Keywords: RML; brain genes; lipopolysaccharide; mice; prion.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Genes differentially expressed in the brain of mice terminally sick that were euthanized after treatment with: (1) resistant mouse recombinant prion protein (moPrPres); (2) moPrPres and lipopolysaccharide (LPS) from Escherichia coli 0111:B4; (3) Rocky mountain Lab brain homogenate (RML); (4) combination of RML and LPS.
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