The present study had several salient findings suggesting that a failure of the antioxidant mechanism may be critical to the environmental effect on schizophrenia onset. Specifically, (i) PWSI augmented cortical ROS production in Ppp1r2-cre/fGluN1 KO mice; (ii) scavenging ROS from the early postnatal period via chronic administration of APO alleviated some of behavioral deficits observed in the KO mice; (iii) oxidative stress was prominent in cortical PV-positive interneurons, a majority of which have genetically eliminated NMDARs; (iv) down-regulation of PGC-1α was associated with a downregulation of PV and increased ROS production. Taken together, these results suggest that failure of antioxidant defense mechanisms in fast-spiking PV interneurons led to excessive ROS production in the cortex, which exacerbates schizophrenia-like behavior in this animal model.
