Age-related changes in mitochondrial active oxygen species production and oxidative damage in brain cortex synaptosomes

ANALIA G. KARADAYIAN; SILVIA LORES ARNAIZ; PAULINA LOMBARDI; JUANITA BUSTAMANTE; FEDERICO ORGAMBIDE

Buenos Aires

Congreso; 2nd FALAN Congress 2016; 2016

Federation of Latinamerican Neuroscience Societies

Brain aging has been associated with mitochondrial dysfunction and active oxygen species generation at nerve terminals. The aim of this study was to evaluate the susceptibility of brain cortex synaptic mitochondria to age-dependent oxidative damage. Male Swiss mice of 3, 17 or 20 months old were used. Brain cortex synaptosomes were isolated by Ficoll gradient procedures. Superoxide anion levels and hydrogen peroxide (H2O2)production were assayed. Also, changes in mitochondrial membrane potential and UCP-2 protein expression were evaluated. At 17 months of age, superoxide levels were 19% lower than in young animals while an increment of 24% was found in synaptosomes from 20 months-old mice. On the other hand, H2O2 production was unaffected at 17 months, but decreased by37% in 20 months old mice. High levels of oxidized cardiolipin were found in synaptosomes from old mice, reflecting that lipid peroxidation increases with age.A significant depolarization was observed in synaptosomes from 20 months-old mice, while no significant changes were found in mitochondrial membrane potential from 17 months-old animals. UCP-2 expression was 61% and 14% increased in synaptosomes from 17- and 20-months old mice respectively compared with young animals.The results of this study suggest that oxidative damage to mitochondria in nerve terminals from brain cortex would increase with age. Regulatory mechanisms such as those mediated by UCP would be overwhelmed at an advanced age.