NEIL1 and NEIL2 DNA glycosylases modulate anxiety and learning in a cooperative manner in mice.

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. © 2021. The Author(s).

Citation

Gunn A Hildrestrand, Veslemøy Rolseth, Nicolas Kunath, Rajikala Suganthan, Vidar Jensen, Anna M Bugaj, Marion S Fernandez-Berrocal, Sunniva B Sikko, Susanne Vetlesen, Anna Kuśnierczyk, Ann-Karin Olsen, Kristine B Gützkow, Alexander D Rowe, Wei Wang, Olve Moldestad, Monica D Syrstad, Geir Slupphaug, Lars Eide, Arne Klungland, Pål Sætrom, Luisa Luna, Jing Ye, Katja Scheffler, Magnar Bjørås. NEIL1 and NEIL2 DNA glycosylases modulate anxiety and learning in a cooperative manner in mice. Communications biology. 2021 Dec 02;4(1):1354

Mesh Tags

Substances

PMID: 34857879

search → result