title: Mitochondrial DNA modifies cognition in interaction with the nuclear genome and age in mice.
abstract: Several lines of evidence indicate an association between mitochondrial DNA (mtDNA) and the functioning of the nervous system. As neuronal development and structure as well as axonal and synaptic activity involve mitochondrial genes, it is not surprising that most mtDNA diseases are associated with brain disorders. Only one study has suggested an association between mtDNA and cognition, however. Here we provide direct evidence of mtDNA involvement in cognitive functioning. Total substitution of mtDNA was achieved by 20 repeated backcrosses in NZB/BlNJ (N) and CBA/H (H) mice with different mtDNA origins. All 13 mitochondrial genes were expressed in the brains of the congenic quartet. In interaction with nuclear DNA (nDNA), mtDNA modified learning, exploration, sensory development and the anatomy of the brain. The effects of mtDNA substitution persisted with age, increasing in magnitude as the mice got older. We observed different effects with input of mtDNA from N versus H mice, varying according to the phenotypes. Exchanges of mtDNA may produce phenotypes outside the range of scores observed in the original mitochondrial and nuclear combinations. These findings show that mitochondrial polymorphisms are not as neutral as was previously believed.
authors.affiliation: CNRS Génétique, Neurogénétique, Comportement, Orléans, France. rouber@lnf.cnrs-mrs.fr
authors.forename: Pierre L
authors.initials: PL
authors.lastname: Roubertoux
authors.forename: Frans
authors.initials: F
authors.lastname: Sluyter
authors.forename: Michèle
authors.initials: M
authors.lastname: Carlier
authors.forename: Brice
authors.initials: B
authors.lastname: Marcet
authors.forename: Fatima
authors.initials: F
authors.lastname: Maarouf-Veray
authors.forename: Chabane
authors.initials: C
authors.lastname: Chérif
authors.forename: Charlotte
authors.initials: C
authors.lastname: Marican
authors.forename: Patricia
authors.initials: P
authors.lastname: Arrechi
authors.forename: Fabienne
authors.initials: F
authors.lastname: Godin
authors.forename: Marc
authors.initials: M
authors.lastname: Jamon
authors.forename: Bernard
authors.initials: B
authors.lastname: Verrier
authors.forename: Charles
authors.initials: C
authors.lastname: Cohen-Salmon
mesh_terms: D000374:Aggression / Q000502:physiology; D000375:Aging / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000502:physiology; D002467:Cell Nucleus / Q000235:genetics; D003071:Cognition / Q000502:physiology*; D003433:Crosses, Genetic; D004272:DNA, Mitochondrial / Q000502:physiology*; D005260:Female; D016678:Genome; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D008928:Mitochondria / Q000235:genetics / Q000502:physiology; D008969:Molecular Sequence Data
chemical_list: D004272:DNA, Mitochondrial