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This Article Full Text Full Text (PDF) All Versions of this Article: 294/2/R501    most recent 00492.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Navarro, A. Articles by Boveris, A. Search for Related Content PubMed PubMed Citation Articles by Navarro, A. Articles by Boveris, A.

DEVELOPMENTAL PHYSIOLOGY AND PREGNANCY

Hippocampal mitochondrial dysfunction in rat aging

Departments of ¹Biochemistry and Molecular Biology and ²Cell Biology and Histology, School of Medicine, University of Cádiz, Cádiz, Spain; ³Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California; and ⁴School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina

Submitted 8 July 2007 ; accepted in final form 7 December 2007

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.

mitochondrial nitric oxide synthase; reduced nicotinamide adenide dinucleotide dehydrogenase; cytochrome oxidase; oxidative damage