Hippocampal mitochondrial dysfunction in rat aging.
Hippocampus mitochondrial dysfunction with impaired electron transfer and increased oxidative damage was observed upon rat aging. Hippocampal mitochondria of aged (12 mo) and senescent (20 mo) rats showed, compared with young (4 mo) rats, marked decreases in the rate of state 3 respiration with NAD-dependent substrates (32-51%) and in the activities of mitochondrial complexes I (57-73%) and IV (33-54%). The activity of mitochondrial nitric oxide synthase was also decreased, 53-66%, with age. These losses in enzymatic activity were more marked in the hippocampus than in brain cortex or in whole brain. The histochemical assay of mitochondrial complex IV in the hippocampus showed decreased staining upon aging. Oxidative damage, determined as the mitochondrial content of thiobarbituric-acid reactive substances (TBARS) and protein carbonyls, increased in aged and senescent hippocampus (66-74% in TBARS and 48-96% in carbonyls). A significant statistical correlation was observed between mitochondrial oxidative damage and enzymatic activity. Mitochondrial dysfunction with shortage of energy supply is considered a likely cause of dysfunction in aged hippocampus.
Navarro
Ana
A
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Plaza Fragela 9, 11003-Cádiz, Spain. ana.navarro@uca.es
López-Cepero
José M
JM
Bández
Manuel J
MJ
Sánchez-Pino
María-Jesús
MJ
Gómez
Carmen
C
Cadenas
Enrique
E
Boveris
Alberto
A
D000375:Aging / Q000378:metabolism*; D000818:Animals; D042967:Electron Transport Complex I / Q000378:metabolism; D014450:Electron Transport Complex III / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008928:Mitochondria / Q000201:enzymology; D028361:Mitochondrial Diseases / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009929:Organ Size; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D017392:Thiobarbituric Acid Reactive Substances; D009243:NAD; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III