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- Ali 2015 Abstract MiPschool Cape Town 2015 + (Mitochondrial dysfunction and oxidative st … Mitochondrial dysfunction and oxidative stress are proposed as key</br>elements in the pathogenesis of aging, as well as neurological and</br>cardiovascular disorders that occur early in life. Sex differences in free</br>radical homeostasis upon aging have been extensively studied. However,</br>little is known about gender differences in mitochondrial function and</br>dynamics of ROS sources that may develop in young ages and hence</br>contribute to sexual dimorphism in some disorders that occur early in</br>life. We investigated heart and brain mitochondrial respiratory function</br>and ROS production in young (2-5 months) male and female wild-type</br>C57BL6 mice using the Oroboros Oxygraph-2k. Mitochondrial respiratory activity</br>in heart did not significantly differ between genders. However, female</br>brains had an enhanced mitochondrial respiratory activity during state</br>3, state 4, and maximally uncoupled respiration as compared to male</br>brains. This respiratory activity observed in mitochondria from female</br>heart and brain was associated with lower rates of hydrogen peroxide</br>production in cardiac and neuronal female mitochondria as compared to</br>male. By using two different approaches, we also found that superoxide</br>dismutase (Sod) activity was higher in female brains, suggesting that</br>enhanced antioxidant defenses in female brains contribute to gender</br>differences in ROS levels. Neither protein expression of NADPH oxidases</br>(Nox2 & Nox4) in brain homogenate or synaptosomes, nor the Oroboros determined</br>activity of these enzymes changed between genders.</br>Paradoxically, when Nox-superoxide was assessed in synaptosomes</br>using spin trapping electron paramagnetic resonance spectroscopy,</br>males exhibited higher activity. We conclude that gender differences in</br>mitochondrial function and ROS production occur in young age, and that</br>differences in antioxidant buffering capacity between genders may be</br>primarily responsible for gender differences in brain ROS homeostasis.r gender differences in brain ROS homeostasis.)