Age-related changes in H2O2 production and bioenergetics in rat brain synaptosomes

Abstract

Detrimental changes to mitochondrial function have been shown to occur with age. In this study we examined the levels of H2O2 production, in situ mitochondrial membrane potential (Δψm), oxygen consumption (JO2) and electron transport chain (ETC) enzyme activities in synaptosomes isolated from rats of two age groups, 6 and 18 months. The rate of H2O2 production in synaptosomes was found to be higher in the 18-month old group compared to that of 6-month old. Δψm was found to be significantly lower in synaptosomes from the older rats, which also correlated with a reduction in JO2. Measurement of the individual electron transport chain enzyme activities revealed that reduced complex II/III and complex IV activities were the possible contributors to the reduced bioenergetic function in synaptosomes from the older rats. These data suggest that ageing may lead to increased nerve terminal H2O2 production while simultaneous deleterious effects on bioenergetic function occur in in situ synaptosomal mitochondria. In addition, Ca2+-independent glutamate release was found to be increased at lower levels of complex I inhibition in the synaptosomes from older rats, suggesting that reduction of mitochondrial function may potentiate excitotoxic conditions in the ageing brain.