title: Hippocampal adult neurogenesis is maintained by Neil3-dependent repair of oxidative DNA lesions in neural progenitor cells.
abstract: Accumulation of oxidative DNA damage has been proposed as a potential cause of age-related cognitive decline. The major pathway for removal of oxidative DNA base lesions is base excision repair, which is initiated by DNA glycosylases. In mice, Neil3 is the main DNA glycosylase for repair of hydantoin lesions in single-stranded DNA of neural stem/progenitor cells, promoting neurogenesis. Adult neurogenesis is crucial for maintenance of hippocampus-dependent functions involved in behavior. Herein, behavioral studies reveal learning and memory deficits and reduced anxiety-like behavior in Neil3(-/-) mice. Neural stem/progenitor cells from aged Neil3(-/-) mice show impaired proliferative capacity and reduced DNA repair activity. Furthermore, hippocampal neurons in Neil3(-/-) mice display synaptic irregularities. It appears that Neil3-dependent repair of oxidative DNA damage in neural stem/progenitor cells is required for maintenance of adult neurogenesis to counteract the age-associated deterioration of cognitive performance.
authors.affiliation: Department of Anatomy, Centre for Molecular Biology and Neuroscience, University of Oslo, N-0317 Oslo, Norway.
authors.forename: Christine Elisabeth
authors.initials: CE
authors.lastname: Regnell
authors.forename: Gunn Annette
authors.initials: GA
authors.lastname: Hildrestrand
authors.forename: Yngve
authors.initials: Y
authors.lastname: Sejersted
authors.forename: Tirill
authors.initials: T
authors.lastname: Medin
authors.forename: Olve
authors.initials: O
authors.lastname: Moldestad
authors.forename: Veslemøy
authors.initials: V
authors.lastname: Rolseth
authors.forename: Silje Zandstra
authors.initials: SZ
authors.lastname: Krokeide
authors.forename: Rajikala
authors.initials: R
authors.lastname: Suganthan
authors.forename: Luisa
authors.initials: L
authors.lastname: Luna
authors.forename: Magnar
authors.initials: M
authors.lastname: Bjørås
authors.forename: Linda H
authors.initials: LH
authors.lastname: Bergersen
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000378:metabolism; D001522:Behavior, Animal / Q000502:physiology; D003071:Cognition / Q000502:physiology; D004249:DNA Damage; D004260:DNA Repair / Q000502:physiology*; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology*; D010084:Oxidation-Reduction
chemical_list: D009419:Nerve Tissue Proteins; D004706:Endodeoxyribonucleases; C540052:NEIL3 protein, mouse