title: Transient OGG1, APE1, PARP1 and Polβ expression in an Alzheimer's disease mouse model.
abstract: Alzheimer's disease (AD) is a disease of major public health significance, whose pathogenesis is strongly linked to the presence of fibrillar aggregates of amyloid-beta (Aβ) in the aging human brain. We exploited the transgenic (Tg)-ArcSwe mouse model for human AD to explore whether oxidative stress and the capacity to repair oxidative DNA damage via base excision repair (BER) are related to Aβ pathology in AD. Tg-ArcSwe mice express variants of Aβ, accumulating senile plaques at 4-6 months of age, and develop AD-like neuropathology as adult animals. The relative mRNA levels of genes encoding BER enzymes, including 8-oxoguanine glycosylase (OGG1), AP endonuclease 1 (APE1), polymerase β (Polβ) and poly(ADP-ribose) polymerase 1 (PARP1), were quantified in various brain regions of 6 weeks, 4 months and 12 months old mice. The results show that OGG1 transcriptional expression was higher, and APE1 expression lower, in 4 months old Tg-ArcSwe than in wildtype (wt) mice. Furthermore, Polβ transcriptional expression was significantly lower in transgenic 12 months old mice than in wt. Transcriptional profiling also showed that BER repair capacity vary during the lifespan in Tg-ArcSwe and wt mice. The BER expression pattern in Tg-ArcSwe mice thus reflects responses to oxidative stress in vulnerable brain structures.
authors.affiliation: Centre for Molecular Biology and Neuroscience, Department of Microbiology, Oslo University Hospital, Norway.
authors.forename: Meryl S
authors.initials: MS
authors.lastname: Lillenes
authors.forename: Mari
authors.initials: M
authors.lastname: Støen
authors.forename: Marta
authors.initials: M
authors.lastname: Gómez-Muñoz
authors.forename: Reidun
authors.initials: R
authors.lastname: Torp
authors.forename: Clara-Cecilie
authors.initials: CC
authors.lastname: Günther
authors.forename: Lars N G
authors.initials: LN
authors.lastname: Nilsson
authors.forename: Tone
authors.initials: T
authors.lastname: Tønjum
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D004249:DNA Damage; D045647:DNA Glycosylases / Q000096:biosynthesis* / Q000235:genetics; D019951:DNA Polymerase beta / Q000096:biosynthesis* / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000096:biosynthesis* / Q000235:genetics; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D009419:Nerve Tissue Proteins; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D019951:DNA Polymerase beta; D045647:DNA Glycosylases; C485990:Ogg1 protein, mouse; C486216:Apex1 protein, mouse; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase
keywords: Alzheimer's disease; AβPP mutation; Base excision repair (BER); DNA repair; OGG1, APE1, PARP1, Polβ; Transgenic (Tg-ArcSwe) mice