Submitted on July 8, 2007
Accepted on December 7, 2007
HIPPOCAMPAL MITOCHONDRIAL DYSFUNCTION IN RAT AGING
Ana Navarro1*, Jose M Lopez-Cepero2, Manuel J. Bandez1, Maria-Jesus Sanchez-Pino1, Carmen Gomez1, Enrique Cadenas3, and Alberto A Boveris4
1 Department of Biochemistry and Molecular Biology, University of Cadiz, School of Medicine, Cadiz, Spain
2 Department of Cell Biology and Histology, University of Cadiz, School of Medicine, Cadiz, Spain
3 Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, California, United States
4 Laboratory of Free Radical Biology, University of Buenos Aires, School of Pharmacy and Biochemistry, Buenos Aires, Argentina
* To whom correspondence should be addressed. E-mail: ana.navarro{at}uca.es.
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, as 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 mtNOS (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 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.
