Mayer, JohannesReichart, GesineTokay, TursonjanLange, FalkoBaltrusch, SimoneJunghanss, ChristianWolkenhauer, OlafJaster, RobertKunz, ManfredTiedge, MarkusIbrahim, SalehFuellen, GeorgKöhling, Rüdiger2016-02-032016-02-032015-04-15Mayer J, Reichart G, Tokay T, Lange F, Baltrusch S, Junghanss C, et al. (2015) Reduced Adolescent-Age Spatial Learning Ability Associated with Elevated Juvenile-Age Superoxide Levels in Complex I Mouse Mutants. PLoS ONE 10(4): e0123863. doi:10.1371/journal.pone.0123863http://nur.nu.edu.kz/handle/123456789/1134Large-scale, heteroplasmic and generally pathogenic mtDNA defects (as induced by defective mitochondrial DNA polymerase, clonal mutations or DNA deletions) are known to negatively impact on life span and can result in apoptosis and tissue loss in, e.g., skeletal muscle or reduce learning abilities. The functional impact of homoplasmic specific mtDNA point mutations, e.g., in genes coding for the electron transport chain, however, remains a matter of debate. The present study contributes to this discussion and provides evidence that a single point mutation in complex I of the respiratory chain is associated with impairment of spatial navigation in adolescent (6-month-old) mice, i.e., reduced performance in the Morris Water Maze, which goes along with increased production of reactive oxygen species (ROS) in juvenile mice (3 months) but not at the age of phenotype expression. A point mutation in complex III goes along with only a mild and non-significant negative effect on cognitive performance and no significant changes in ROS production. These findings suggest to also consider the ontogenetic development of phenotypes when studying mtDNA mutations and highlights a possible impact of complex I dysfunction on the emergence of neurological deficits.enAttribution-NonCommercial-NoDerivs 3.0 United StatesArticle