Mitochondrial dysfunction: maternal protein restriction as a trigger of reactive species overproduction and brainstem energy failure in male offspring brainstem

Abstract

Mitochondria are important organelles in eukaryotic organisms, wherein their capacity to produce energy vary among the tissues depending upon the amounts of oxygen consumed. Part of the oxygen consumed during ATP generation produces reactive oxygen species, which if not efficiently removed can trigger a systemic damage to molecular compounds characterized as oxidative stress. Several studies have demonstrated that mitochondrial dysfunction and oxidative stress in the central nervous system (CNS) are related to a plethora of neural disorders. Herein, we hypothesize that a late autonomic imbalance-induced hypertension might be related to long-lasting effects of protein restriction during the critical period of the CNS development on the mitochondrial function and oxidative stress in the brainstem of adult (i.e. 150 days of age) male Wistar rats. Maternal protein restriction was induced by offering a diet based on 8% of casein from first day of pregnancy until weaning, when the male pups started to receive laboratory chow up to 150 days of life. The protein restriction induced an extended detrimental modulation in mitochondria function, decreasing the phosphorylation capacity with concomitant decrease in the mitochondrial membrane potential, wherein the reactive species overproduction triggered a disruption in proton conductance, which may gradually compromise mitochondria energy conservation. Interestingly, the elevated activity of glutathione-S-transferase and the augmented expression of uncoupling protein 2 are likely protective mechanisms induced by lipid peroxidation products, being feasible molecular changes attempting to deal with oxidative stress-induced ageing.