title: Increased learning and brain long-term potentiation in aged mice lacking DNA polymerase μ.
abstract: 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.
authors.affiliation: Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Madrid, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lucas
authors.forename: José M
authors.initials: JM
authors.lastname: Delgado-García
authors.forename: Beatriz
authors.initials: B
authors.lastname: Escudero
authors.forename: Carmen
authors.initials: C
authors.lastname: Albo
authors.forename: Ana
authors.initials: A
authors.lastname: Aza
authors.forename: Rebeca
authors.initials: R
authors.lastname: Acín-Pérez
authors.forename: Yaima
authors.initials: Y
authors.lastname: Torres
authors.forename: Paz
authors.initials: P
authors.lastname: Moreno
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Enríquez
authors.forename: Enrique
authors.initials: E
authors.lastname: Samper
authors.forename: Luis
authors.initials: L
authors.lastname: Blanco
authors.forename: Alfonso
authors.initials: A
authors.lastname: Fairén
authors.forename: Antonio
authors.initials: A
authors.lastname: Bernad
authors.forename: Agnès
authors.initials: A
authors.lastname: Gruart
mesh_terms: D000375:Aging; D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism / Q000502:physiology*; D003214:Conditioning, Classical; D004247:DNA / Q000235:genetics; D004260:DNA Repair; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D007858:Learning; D008124:Locomotion; D017774:Long-Term Potentiation / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress; D010641:Phenotype; D015203:Reproducibility of Results; D013696:Temperature
chemical_list: D004247:DNA; C407743:DNA polymerase mu; D004259:DNA-Directed DNA Polymerase