Maternal immune activation leads to increased nNOS immunoreactivity in the brain of postnatal day 2 rat offspring

Neuronal nitric oxide synthase (nNOS) is a key arginine metabolising enzyme in the brain, and nNOS-derived nitric oxide (NO) plays an important role in regulating glutamatergic neurotransmission. NO and its related molecules are involved in the pathogenesis of schizophrenia, and human genetic studies have identified schizophrenia risk genes encoding nNOS. This study systematically investigated how maternal immune activation (MIA; a risk factor for schizophrenia) induced by polyinosinic:polycytidylic acid affected nNOS-immunoreactivity in the brain of the resulting male and female offspring at the age of postnatal day (PND) 2. Immunohistochemistry revealed a markedly increased intensity of nNOS-positive cells in the CA3 and dentate gyrus subregions of the hippocampus, the somatosensory cortex, and the striatum, but not the frontal cortex and hippocampal CA1 region, in the MIA offspring when compared to control group animals. There were no sex differences in the effect. Given the role of nNOS in glutamatergic neurotransmission and its functional relationship with glutamate NMDA receptors, increased nNOS immunoreactivity may indicate the up-regulation of NMDA receptor function in MIA rat offspring at an early postnatal age. Future research is required to determine whether these changes contribute to the neuronal and behavioral dysfunction observed in both juvenile and adult MIA rat offspring.