CONICET | Buscador de Institutos y Recursos Humanos

During aging, changes in brain cortex mitochondrial bioenergetics and in active oxygen species generation have been extensively described. Previous results from our laboratory showed impairment of mitochondrial respiratory chain in aged mice. The susceptibility of brain cortex synaptic mitochondria to age-dependent oxidative damage was studied in 3 and 17 months oldmice. Synaptosomal fractions were isolated by Ficoll gradient procedures. Active oxygen species superoxide anion levels and hydrogen peroxide (H2O2)production were assayed. Also, cardiolipin oxidation, UCP-2 expression and enzyme activities of monoamino oxidase (MAO) and acetylcholinesterase were determined.At 17 months of age, superoxide levels were 19% lower than in young animals, while H2O2 production increased by 32%. In the presence of the MAO inhibitor deprenyl, H2O2 production was not affected, suggesting that the increase in H2O2 could be due to MAO activity. This enzyme activity was 62% increased in synaptosomes from 17-months old mice. Intact cardiolipin content was 42% lower in synaptosomes from old mice, reflecting an increase in cardiolipin oxidation with age. UCP-2 expression was 61%increased in synaptosomes from 17-months old mice compared with young animals.An increase of 57% in acetylcholinesterase activity was observed in synaptosomes from old mice. The results of this study suggest that oxidative damage to mitochondria in nerve terminals from brain cortex would be caused by an increase in H2O2 generation with age.The increase in UCP expression would provide a regulatory mechanism to maintain low superoxide levels. H2O2 production would be a consequence of both MAO activity and mitochondrial respiratory chain (derived from superoxide). Our results suggest that the increment in H2O2 levels would be due to MAO increase with age.