Brain cortex mitochondrial bioenergetics in synaptosomes and non-synaptic mitochondria during aging
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Alterations in mitochondrial bioenergetics have been associated with brain aging. In order to evaluate the susceptibility of brain cortex synaptosomes and non-synaptic mitochondria to aging-dependent dysfunction, male Swiss mice of 3 or 17 months old were used. Mitochondrial function was evaluated by oxygen consumption, mitochondrial membrane potential and respiratory complexes activity, together with UCP-2 protein expression. Basal respiration and respiration driving proton leak were decreased by 26 and 33 % in synaptosomes from 17-months old mice, but spare respiratory capacity was not modified by aging. Succinate supported state 3 respiratory rate was decreased by 45 % in brain cortex non-synaptic mitochondria from 17-month-old mice, as compared with young animals, but respiratory control was not affected. Synaptosomal mitochondria would be susceptible to undergo calcium-induced depolarization in 17 months-old mice, while non-synaptic mitochondria would not be affected by calcium overload. UCP-2 was significantly up-regulated in both synaptosomal and submitochondrial membranes from 17-months old mice, compared to young animals. UCP-2 upregulation seems to be a possible mechanism by which mitochondria would be resistant to suffer oxidative damage during aging.
KeywordsSynaptosomes Non-synaptic mitochondria Aging Cerebral cortex Respiration Depolarization
Central nervous system
Cytochrome c oxidase
Carbonyl cyanide p-trifluoromethoxyphenylhydrazone
Forward side scatter
Mitochondrial permeability transition
Respiratory control rate
Reactive oxygen species
Voltage-dependent anion channel
This research was supported by Grants from Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET, PIP 112-20110100271), and Universidad de Buenos Aires (UBA, 0020130100255BA), Argentina.
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