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Open AccessArticle

Glutathione Deficiency and Alterations in the Sulfur Amino Acid Homeostasis during Early Postnatal Development as Potential Triggering Factors for Schizophrenia-Like Behavior in Adult Rats

1
The Chair of Medical Biochemistry, Jagiellonian University Medical College, 7 Kopernika Street, 31–034 Kraków, Poland
2
Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31–343 Kraków, Poland
3
Department of Environmental Chemistry, University of Łódź, 163 Pomorska Street, 90-236 Łódź, Poland
*
Author to whom correspondence should be addressed.
Academic Editor: Peter Rose
Molecules 2019, 24(23), 4253; https://doi.org/10.3390/molecules24234253
Received: 10 October 2019 / Revised: 15 November 2019 / Accepted: 18 November 2019 / Published: 22 November 2019
(This article belongs to the Special Issue Sulfur Compounds and Human Health)
Impaired glutathione (GSH) synthesis and dopaminergic transmission are important factors in the pathophysiology of schizophrenia. Our research aimed to assess the effects of l-buthionine-(S,R)-sulfoximine (BSO), a GSH synthesis inhibitor, and GBR 12909, a dopamine reuptake inhibitor, administered alone or in combination, to Sprague–Dawley rats during early postnatal development (p5–p16), on the levels of GSH, sulfur amino acids, global DNA methylation, and schizophrenia-like behavior. GSH, methionine (Met), homocysteine (Hcy), and cysteine (Cys) contents were determined in the liver, kidney, and in the prefrontal cortex (PFC) and hippocampus (HIP) of 16-day-old rats. DNA methylation in the PFC and HIP and schizophrenia-like behavior were assessed in adulthood (p90–p93). BSO caused the tissue-dependent decreases in GSH content and alterations in Met, Hcy, and Cys levels in the peripheral tissues and in the PFC and HIP. The changes in these parameters were accompanied by alterations in the global DNA methylation in the studied brain structures. Parallel to changes in the global DNA methylation, deficits in the social behaviors and cognitive functions were observed in adulthood. Only BSO + GBR 12909-treated rats exhibited behavioral alterations resembling positive symptoms in schizophrenia patients. Our results suggest the usefulness of this neurodevelopmental model for research on the pathomechanism of schizophrenia. View Full-Text
Keywords: social and cognitive deficits; GSH deficiency; global DNA methylation; neurodevelopmental model of schizophrenia; sulfur amino acids levels social and cognitive deficits; GSH deficiency; global DNA methylation; neurodevelopmental model of schizophrenia; sulfur amino acids levels
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Górny, M.; Wnuk, A.; Kamińska, A.; Kamińska, K.; Chwatko, G.; Bilska-Wilkosz, A.; Iciek, M.; Kajta, M.; Rogóż, Z.; Lorenc-Koci, E. Glutathione Deficiency and Alterations in the Sulfur Amino Acid Homeostasis during Early Postnatal Development as Potential Triggering Factors for Schizophrenia-Like Behavior in Adult Rats. Molecules 2019, 24, 4253.

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