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

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• 作者：Seá ; n M. Kilbride ; Jayne E. Telford ; Gavin P. Davey
• 关键词：Synaptosomes ; Mitochondria ; Ageing ; Reactive oxygen species ; Complex 1
• 刊名：Biochimica et Biophysica Acta (BBA)/Bioenergetics
• 出版年：2008
• 出版时间：July-August 2008
• 年：2008
• 卷：1777
• 期：7-8
• 页码：783-788
• 全文大小：492 K

文摘

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 (Δψ_m), 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. Δψ_m 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.