title: Alzheimer's disease-like pathology in senescence-accelerated OXYS rats can be partially retarded with mitochondria-targeted antioxidant SkQ1.
abstract: We previously showed that mitochondria-targeted antioxidant SkQ1 (plastoquinonyl-decyltriphenylphosphonium) at nanomolar concentrations is capable of preventing and slowing down some cerebral dysfunctions in accelerated-senescence OXYS rats. Here we demonstrate that OXYS rats develop behavior, learning, and memory deficits against a background of neurodegeneration signs detected by magnetic resonance tomography and amyloid-β (Aβ) pathology similar to those seen in Alzheimer's disease (AD). Long-term treatment with SkQ1 (250 nmol/kg body weight daily from the age of 1.5 to 23 months) reduced the age-related alterations in behavior and spatial memory deficit in Morris water maze in OXYS and Wistar rats. Furthermore, this is the first report that SkQ1 treatment slows down pathological accumulation of AβPP, Aβ, and hyperphosphorylation of tau-protein in OXYS rats, as well as age-dependent changes in healthy Wistar rats. Our results support the possibility of using the OXYS strain as a rat model of AD-like pathology. It seems probable that the mitochondria-targeted antioxidant SkQ1 can be a good prophylactic strategy to maintain brain health and to treat AD.
authors.affiliation: Institute of Cytology and Genetics, Novosibirsk, Russia.
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Stefanova
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Muraleva
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Skulachev
authors.forename: Nataliya G
authors.initials: NG
authors.lastname: Kolosova
mesh_terms: D000367:Age Factors; D000375:Aging / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy* / Q000473:pathology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology; D004195:Disease Models, Animal; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy / Q000209:etiology; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D010971:Plastoquinone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011922:Rats, Mutant Strains; D017208:Rats, Wistar; D013028:Space Perception / Q000187:drug effects
chemical_list: D000975:Antioxidants; D010971:Plastoquinone
keywords: Alzheimer's disease; brain aging; mitochondria-targeted antioxidant SkQ1; senescence-accelerated OXYS rats