title: Reduced adolescent-age spatial learning ability associated with elevated juvenile-age superoxide levels in complex I mouse mutants.
abstract: Large-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.
authors: Oscar-Langendorff-Institute of Physiology, Rostock University Medical Center, Rostock, Germany.
authors: Johannes
authors: J
authors: Mayer
authors: Oscar-Langendorff-Institute of Physiology, Rostock University Medical Center, Rostock, Germany.
authors: Gesine
authors: G
authors: Reichart
authors: Oscar-Langendorff-Institute of Physiology, Rostock University Medical Center, Rostock, Germany; Center for Life Sciences, Nazarbayev University, Astana, Republic of Kazakhstan.
authors: Tursonjan
authors: T
authors: Tokay
authors: Oscar-Langendorff-Institute of Physiology, Rostock University Medical Center, Rostock, Germany.
authors: Falko
authors: F
authors: Lange
authors: Institute of Medical Biochemistry and Molecular Biology, Rostock University Medical Center, Rostock, Germany.
authors: Simone
authors: S
authors: Baltrusch
authors: Department of Hematology/Oncology/Palliative Medicine, Rostock University Medical Center, Rostock, Germany.
authors: Christian
authors: C
authors: Junghanss
authors: Department of Systems Biology and Bioinformatics, University of Rostock, Rostock, Germany.
authors: Olaf
authors: O
authors: Wolkenhauer
authors: Division of Gastroenterology, Department of Medicine II, Rostock University Medical Center, Rostock, Germany.
authors: Robert
authors: R
authors: Jaster
authors: Department of Dermatology, Venereology and Allergology, University of Leipzig, Leipzig, Germany.
authors: Manfred
authors: M
authors: Kunz
authors: Institute of Medical Biochemistry and Molecular Biology, Rostock University Medical Center, Rostock, Germany.
authors: Markus
authors: M
authors: Tiedge
authors: Department of Dermatology, Lübeck University Medical Center, Lübeck, Germany.
authors: Saleh
authors: S
authors: Ibrahim
authors: Institute for Biostatistics and Informatics in Medicine and Ageing Research, Rostock, Germany; Interdisciplinary Faculty, University of Rostock, Rostock, Germany.
authors: Georg
authors: G
authors: Fuellen
authors: Oscar-Langendorff-Institute of Physiology, Rostock University Medical Center, Rostock, Germany; Interdisciplinary Faculty, University of Rostock, Rostock, Germany.
authors: Rüdiger
authors: R
authors: Köhling
mesh_terms: D000818:Animals; D003071:Cognition; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D042967:Electron Transport Complex I / Q000235:genetics* / Q000378:metabolism; D014450:Electron Transport Complex III / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D008297:Male; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009949:Orientation / Q000502:physiology; D017354:Point Mutation; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013028:Space Perception / Q000502:physiology
chemical_list: D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III