Communications biology · 2021
NEIL1 and NEIL2 DNA glycosylases modulate anxiety and learning in a cooperative manner in mice.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Hildrestrand Gunn A, Rolseth Veslemøy, Kunath Nicolas, Suganthan Rajikala, Jensen Vidar, Bugaj Anna M, Fernandez-Berrocal Marion S, Sikko Sunniva B, Vetlesen Susanne, Kuśnierczyk Anna, Olsen Ann-Karin, Gützkow Kristine B, Rowe Alexander D, Wang Wei, Moldestad Olve, Syrstad Monica D, Slupphaug Geir, Eide Lars, Klungland Arne, Sætrom Pål, Luna Luisa, Ye Jing, Scheffler Katja, Bjørås Magnar
Аннотация
Oxidative DNA damage in the brain has been implicated in neurodegeneration and cognitive decline. DNA glycosylases initiate base excision repair (BER), the main pathway for oxidative DNA base lesion repair. NEIL1 and NEIL3 DNA glycosylases affect cognition in mice, while the role of NEIL2 remains unclear. Here, we investigate the impact of NEIL2 and its potential overlap with NEIL1 on behavior in knockout mouse models. Neil1-/-Neil2-/- mice display hyperactivity, reduced anxiety and improved learning. Hippocampal oxidative DNA base lesion levels are comparable between genotypes and no mutator phenotype is found. Thus, impaired canonical repair is not likely to explain the altered behavior. Electrophysiology suggests reduced axonal activation in the hippocampal CA1 region in Neil1-/-Neil2-/- mice and lack of NEIL1 and NEIL2 causes dysregulation of genes in CA1 relevant for synaptic function. We postulate a cooperative function of NEIL1 and NEIL2 in genome regulation, beyond canonical BER, modulating behavior in mice.