Maternal immune activation (MIA) is an important risk factor for neurodevelopmental disorders such as autism. The aim of the current study was to investigate the development-dependent changes in the mitochondrial function of MIA-exposed offspring, which may contribute to autism-like deficits. MIA was evoked by the single intraperitoneal administration of lipopolysaccharide to pregnant rats at gestation day 9.5, and several aspects of mitochondrial function in fetuses and in the brains of seven-day-old pups and adolescent offspring were analyzed along with oxidative stress parameters measurement. It was found that MIA significantly increased the activity of NADPH oxidase (NOX), an enzyme generating reactive oxygen species (ROS) in the fetuses and in the brain of seven-day-old pups, but not in the adolescent offspring. Although a lower mitochondrial membrane potential accompanied by a decreased ATP level was already observed in the fetuses and in the brain of seven-day-old pups, persistent alterations of ROS, mitochondrial membrane depolarization, and lower ATP generation with concomitant electron transport chain complexes downregulation were observed only in the adolescent offspring. We suggest that ROS observed in infancy are most likely of a NOX activity origin, whereas in adolescence, ROS are produced by damaged mitochondria. The accumulation of dysfunctional mitochondria leads to the intense release of free radicals that trigger oxidative stress and neuroinflammation, resulting in an interlinked vicious cascade.
Keywords: NADPH oxidase; ROS; animal model; autism; maternal immune activation; mitochondria; neurodevelopmental disorders.