title: Synergistic Actions of Ogg1 and Mutyh DNA Glycosylases Modulate Anxiety-like Behavior in Mice.
abstract: Ogg1 and Mutyh DNA glycosylases cooperate to prevent mutations caused by 8-oxoG, a major premutagenic DNA lesion associated with cognitive decline. We have examined behavior and cognitive function in mice deficient of these glycosylases. Ogg1(-/-)Mutyh(-/-) mice were more active and less anxious, with impaired learning ability. In contrast, Mutyh(-/-) mice showed moderately improved memory. We observed no apparent change in genomic 8-oxoG levels, suggesting that Ogg1 and Mutyh play minor roles in global repair in adult brain. Notably, transcriptome analysis of hippocampus revealed that differentially expressed genes in the mutants belong to pathways known to be involved in anxiety and cognition. Esr1 targets were upregulated, suggesting a role of Ogg1 and Mutyh in repression of Esr1 signaling. Thus, beyond their involvement in DNA repair, Ogg1 and Mutyh regulate hippocampal gene expression related to cognition and behavior, suggesting a role for the glycosylases in regulating adaptive behavior.
authors.affiliation: Department of Microbiology, Oslo University Hospital and University of Oslo, 0424 Oslo, Norway.
authors.forename: Monica D
authors.initials: MD
authors.lastname: Bjørge
authors.affiliation: Department of Microbiology, Oslo University Hospital and University of Oslo, 0424 Oslo, Norway.
authors.forename: Gunn A
authors.initials: GA
authors.lastname: Hildrestrand
authors.affiliation: Department of Microbiology, Oslo University Hospital and University of Oslo, 0424 Oslo, Norway; Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway.
authors.forename: Katja
authors.initials: K
authors.lastname: Scheffler
authors.affiliation: Department of Microbiology, Oslo University Hospital and University of Oslo, 0424 Oslo, Norway.
authors.forename: Rajikala
authors.initials: R
authors.lastname: Suganthan
authors.affiliation: Department of Microbiology, Oslo University Hospital and University of Oslo, 0424 Oslo, Norway.
authors.forename: Veslemøy
authors.initials: V
authors.lastname: Rolseth
authors.affiliation: Proteomics and Metabolomics Core Facility PROMEC, Norwegian University of Science and Technology, 7491 Trondheim, Norway.
authors.forename: Anna
authors.initials: A
authors.lastname: Kuśnierczyk
authors.affiliation: Department of Microbiology, Oslo University Hospital and University of Oslo, 0424 Oslo, Norway.
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Rowe
authors.affiliation: Proteomics and Metabolomics Core Facility PROMEC, Norwegian University of Science and Technology, 7491 Trondheim, Norway.
authors.forename: Cathrine B
authors.initials: CB
authors.lastname: Vågbø
authors.affiliation: Department of Microbiology, Oslo University Hospital and University of Oslo, 0424 Oslo, Norway.
authors.forename: Susanne
authors.initials: S
authors.lastname: Vetlesen
authors.affiliation: Department of Medical Biochemistry, Oslo University Hospital and University of Oslo, 0424 Oslo, Norway.
authors.forename: Lars
authors.initials: L
authors.lastname: Eide
authors.affiliation: Proteomics and Metabolomics Core Facility PROMEC, Norwegian University of Science and Technology, 7491 Trondheim, Norway; Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway.
authors.forename: Geir
authors.initials: G
authors.lastname: Slupphaug
authors.affiliation: Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, and Research Center for Nucleotide Pool, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Yusaku
authors.initials: Y
authors.lastname: Nakabeppu
authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Bredy
authors.affiliation: Department of Microbiology, Oslo University Hospital and University of Oslo, 0424 Oslo, Norway.
authors.forename: Arne
authors.initials: A
authors.lastname: Klungland
authors.affiliation: Department of Microbiology, Oslo University Hospital and University of Oslo, 0424 Oslo, Norway; Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway. Electronic address: magnar.bjoras@rr-research.no.
authors.forename: Magnar
authors.initials: M
authors.lastname: Bjørås
mesh_terms: D000818:Animals; D001007:Anxiety / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D045647:DNA Glycosylases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D045647:DNA Glycosylases; C485990:Ogg1 protein, mouse; C061738:mutY adenine glycosylase