Effects of maternal immune activation on brain arginine metabolism of postnatal day 2 rat offspring

l-Arginine is a versatile semi-essential amino acid with a number of bioactive metabolites, and altered arginine metabolism has been implicated in the pathogenesis of schizophrenia. Earlier research has demonstrated that maternal immune activation (MIA; a risk factor for schizophrenia) alters arginine metabolism in the prefrontal cortex and hippocampus of the adult offspring. The present study investigated how MIA affected the levels of l-arginine and its downstream metabolites in the whole forebrain, frontal cortex, hippocampus and cerebellum of male and female rat offspring at the age of postnatal day 2. While no effects were evident in the forebrain, MIA significantly increased l-arginine, glutamate, putrescine, spermidine and spermine levels and the glutamate/GABA ratio, but decreased the glutamine/glutamate ratio, in the frontal cortex, hippocampus and/or cerebellum with no marked sex differences. Cluster analyses revealed that l-arginine and its main metabolites formed distinct groups, which changed as a function of MIA or sex in all four brain regions examined. These results demonstrate, for the first time, that MIA alters brain arginine metabolism in the rat offspring during early neonatal development, and further support the involvement of arginine metabolism in the pathogenesis of schizophrenia.