Highly aggressive behavior induced by social stress is associated to reduced cytochrome c oxidase activity in mice brain cortex

Violence and aggression represent severe social problems, with profound impacts on public health. Despite the development of experimental models to study aggressive behavior is highly appreciated, the underlying mechanisms remain poorly understood. Given the key contribution of mitochondria to central nervous system bioenergetics, we hypothesized that mitochondrial function in brain would be altered by social stress. Using a model of spontaneous aggression, we investigated here the effects of social stress on brain mitochondrial function in prefrontal cortex of Swiss mice. Animals were categorized as highly aggressive, subordinate and non-aggressive (harmonic) after stress induced by regrouping and compared them with non-regrouped animals. Despite social stress did not affect brain cortex oxygen consumption rates and NADH:cytochrome c oxidoreductase activity, cytochrome c oxidase expression and activity were significantly lower in highly aggressive animals compared to non-regrouped ones. These changes were not observed in ATP synthase and adenine nucleotide translocator content suggesting a selective effect of social stress on cytochrome c oxidase. Therefore, aggressive behavior generated upon social stress associates to selective reduction in cytochrome c oxidase activity, with potential detrimental effects on brain bioenergetics and function.