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dc.contributor.authorScheffler, Katja
dc.contributor.authorJalland, Clara Maria Osnes
dc.contributor.authorBenestad, Sylvie L.
dc.contributor.authorMoldal, Torfinn
dc.contributor.authorErsdal, Cecilie
dc.contributor.authorGunnes, Gjermund
dc.contributor.authorSuganthan, Rajikala
dc.contributor.authorBjørås, Magnar
dc.contributor.authorTranulis, Michael A.
dc.identifier.citationFree Radical Biology & Medicine. 2020, 152, 348-354.en_US
dc.description.abstractThe DNA glycosylase Neil2 is a member of the base excision repair (BER) family of enzymes, which are important for repair of oxidative DNA damage. Specifically, Neil2 participates in repair of oxidized bases in single-stranded DNA of transcriptionally active genes. Mice with genetic ablation of Neil2 (Neil2−/−) display no overt phenotypes, but an age-dependent accumulation of oxidative DNA damage and increased inflammatory responsiveness. In young mice intra-cerebrally inoculated with prions, vigorous prion propagation starts rapidly in the germinal follicles of the spleen due to inoculum spillover. Here, we compare experimental prion disease in Neil2−/− mice with that in wild-type mice at disease onset and end-stage. Specifically, we investigated disease progression, accumulation of DNA damage, and mitochondrial respiratory complex activity in brain and spleen. We used genome-wide RNA sequencing of the spleen to compare the immune responses to prion propagation between the two groups of mice, at both onset and end-stage prion disease. The Neil2−/− mice deteriorated more rapidly than wild-type mice after onset of clinical signs. Levels of DNA damage in brain increased in both mouse groups, slightly more in the Neil2−/− mice. Transcriptome data from spleen at disease onset were similar between the mouse groups with moderate genomic responses. However, at end-stage a substantial response was evident in the wild-type mice but not in Neil2−/− mice. Our data show that Neil2 counteracts toxic signaling in clinical prion disease, and this is separate from gross pathological manifestations and PrPSc accumulation.en_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internasjonal*
dc.titleDNA glycosylase Neil2 contributes to genomic responses in the spleen during clinical prion diseaseen_US
dc.typePeer revieweden_US
dc.typeJournal articleen_US
dc.source.journalFree Radical Biology & Medicineen_US

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Attribution-NonCommercial-NoDerivatives 4.0 Internasjonal
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivatives 4.0 Internasjonal