Increased learning and brain long-term potentiation in aged mice lacking DNA polymerase μ

• Published in: PloS one Vol. 8; no. 1; p. e53243
• Main Authors: Lucas, Daniel, Delgado-García, José M, Escudero, Beatriz, Albo, Carmen, Aza, Ana, Acín-Pérez, Rebeca, Torres, Yaima, Moreno, Paz, Enríquez, José Antonio, Samper, Enrique, Blanco, Luis, Fairén, Alfonso, Bernad, Antonio, Gruart, Agnès
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 03.01.2013; Public Library of Science (PLoS)
• Subjects: Ablation; Aging; Animals; Associative learning; Behavior, Animal; Bioinformatics; Biology; Brain; Brain - metabolism; Brain - physiology; Cardiology; Cognitive ability; Conditioning, Classical; Defects; Deoxyribonucleic acid; DNA; DNA - genetics; DNA polymerase; DNA Repair; DNA-directed DNA polymerase; DNA-Directed DNA Polymerase - genetics; DNA-Directed DNA Polymerase - metabolism; Hippocampus - metabolism; Homology; Immunoglobulins; Learning; Locomotion; Long-term potentiation; Long-Term Potentiation - genetics; Male; Mammals; Medicine; Mice; Mice, Knockout; Mitochondria; Nervous system; Non-homologous end joining; Oxidative Stress; Phenotype; Physics; Potentiation; Repair; Reproducibility of Results; Rodents; Social and Behavioral Sciences; Temperature; Transgenic animals; New York; United States > US; Spain
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0053243

A definitive consequence of the aging process is the progressive deterioration of higher cognitive functions. Defects in DNA repair mechanisms mostly result in accelerated aging and reduced brain function. DNA polymerase µ is a novel accessory partner for the non-homologous end-joining DNA repair pathway for double-strand breaks, and its deficiency causes reduced DNA repair. Using associative learning and long-term potentiation experiments, we demonstrate that Polµ(-/-) mice, however, maintain the ability to learn at ages when wild-type mice do not. Expression and biochemical analyses suggest that brain aging is delayed in Polµ(-/-) mice, being associated with a reduced error-prone DNA oxidative repair activity and a more efficient mitochondrial function. This is the first example in which the genetic ablation of a DNA-repair function results in a substantially better maintenance of learning abilities, together with fewer signs of brain aging, in old mice.