Dexamethasone treatment differentially affects the oxidative energy metabolism of rat brain mitochondria in developing and adult animals

Abstract

We studied the effect of repeated exposure to dexamethasone (Dex) treatment on rat brain mitochondrial oxidative energy metabolism in developing rats at different postnatal ages, i.e. 2–5 week and in adults. The animals were injected with a dose of 2mg of Dex/kg body weight at around 7:00 a.m. for three alternative days prior to the day of sacrifice; the control group animals received saline vehicle. We measured rates of respiration with different substrates, viz. glutamate, pyruvate+malate, succinate and ascorbate+TMPD; the contents of individual cytochromes and the dehydrogenases and ATPase activities. Dex treatment, in general, stimulated the state 3 rates of respiration rates in young animals in age-dependent and substrate-specific manner except for the 3 week group, whereas in the adults there was substantial inhibition of the respiration. The pattern of dehydrogenases activities matched with respiration rates. Dex treatment also resulted in uncoupling of the second and third site of phosphorylation in 3-week-old animals and in the adults. The contents of cytochrome aa3, b and ATPase activities decreased significantly after Dex treatment in all the age groups. The results thus emphasize that exposure to repeated Dex treatment can significantly influence the oxidative energy metabolism of brain mitochondria in young growing animals as well as in adults.