Glutathione deficiency in the early postnatal developmental period as a neurodevelopmental animal model of schizophrenia.

The etiopathology of schizophrenia is still poorly understood. Still, it is widely accepted that oxidative stress, particularly during early stages of brain development, is associated with increased risk of developing schizophrenia. Several studies indicate that glutathione (GSH) is a key factor in maintaining redox balance in cells and is involved in numerous metabolic processes. Its deficiency in the neonatal period leads to permanent brain damage, manifested by schizophrenia-like symptoms in adults. Hence, administration of the GSH synthesis inhibitor L-buthionine-(S, R)-sulfoximine (BSO) alone and in co-treatment with the dopamine reuptake inhibitor 1-[2-[Bis-4(fluorophenyl)methoxy]ethyl]-4-3-(3-phenylpropyl) (GBR 12909) to rodents in neonatal period produces good neurodevelopmental models offering an opportunity to examine various neuroanatomical changes and different symptoms in schizophrenia spectrum. Schizophrenia is modeled by inducing lesions or changes in activity in specific brain regions of rodents (primarily the prefrontal cortex and hippocampus). Such artificially induced dysfunctions, discussed in this article, suggest the usefulness of these neurodevelopmental models in research on the pathomechanisms of schizophrenia. The aim of this review is to analyze the literature on the impact of GSH deficiency on the etiopathology of schizophrenia, with particular emphasis on neurodevelopmental animal models in which oxidative stress during early postnatal development causes schizophrenia-like symptoms in adulthood.