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Title

Increased Learning and Brain Long-Term Potentiation in Aged Mice Lacking DNA Polymerase μ

AuthorsLucas, Daniel; Delgado-García, José María; Escudero, Beatriz; Albo, Carmen; Aza, Ana ; Acín-Pérez, Rebeca; Torres, Yaima; Moreno, Paz; Enríquez, José Antonio; Samper, Enrique; Blanco Dávila, Luis; Fairén, Alfonso; Gruart, Agnès; Bernad, Antonio
Issue Date2013
PublisherPublic Library of Science
CitationPLoS ONE 8 (2013)
AbstractA 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 ο 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 Polο-/- 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 Polο-/- 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. © 2013 Lucas et al.
URIhttp://hdl.handle.net/10261/97736
DOI10.1371/journal.pone.0053243
Identifiersdoi: 10.1371/journal.pone.0053243
issn: 1932-6203
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