{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T02:32:20Z","timestamp":1782959540224,"version":"3.54.5"},"reference-count":107,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2019,11,22]],"date-time":"2019-11-22T00:00:00Z","timestamp":1574380800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Centre of Poland","award":["UMO-2016\/23\/B\/NZ7\/01280"],"award-info":[{"award-number":["UMO-2016\/23\/B\/NZ7\/01280"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>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\u2013Dawley rats during early postnatal development (p5\u2013p16), 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\u2013p93). 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.<\/jats:p>","DOI":"10.3390\/molecules24234253","type":"journal-article","created":{"date-parts":[[2019,11,22]],"date-time":"2019-11-22T09:02:52Z","timestamp":1574413372000},"page":"4253","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["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"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6393-9977","authenticated-orcid":false,"given":"Magdalena","family":"G\u00f3rny","sequence":"first","affiliation":[{"name":"The Chair of Medical Biochemistry, Jagiellonian University Medical College, 7 Kopernika Street, 31\u2013034 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3620-3902","authenticated-orcid":false,"given":"Agnieszka","family":"Wnuk","sequence":"additional","affiliation":[{"name":"Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Sm\u0119tna Street, 31\u2013343 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrianna","family":"Kami\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Environmental Chemistry, University of \u0141\u00f3d\u017a, 163 Pomorska Street, 90-236 \u0141\u00f3d\u017a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinga","family":"Kami\u0144ska","sequence":"additional","affiliation":[{"name":"Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Sm\u0119tna Street, 31\u2013343 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9247-5131","authenticated-orcid":false,"given":"Gra\u017cyna","family":"Chwatko","sequence":"additional","affiliation":[{"name":"Department of Environmental Chemistry, University of \u0141\u00f3d\u017a, 163 Pomorska Street, 90-236 \u0141\u00f3d\u017a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9066-6292","authenticated-orcid":false,"given":"Anna","family":"Bilska-Wilkosz","sequence":"additional","affiliation":[{"name":"The Chair of Medical Biochemistry, Jagiellonian University Medical College, 7 Kopernika Street, 31\u2013034 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0422-0428","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"Iciek","sequence":"additional","affiliation":[{"name":"The Chair of Medical Biochemistry, Jagiellonian University Medical College, 7 Kopernika Street, 31\u2013034 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u0142gorzata","family":"Kajta","sequence":"additional","affiliation":[{"name":"Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Sm\u0119tna Street, 31\u2013343 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zofia","family":"Rog\u00f3\u017c","sequence":"additional","affiliation":[{"name":"Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Sm\u0119tna Street, 31\u2013343 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9970-8548","authenticated-orcid":false,"given":"El\u017cbieta","family":"Lorenc-Koci","sequence":"additional","affiliation":[{"name":"Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Sm\u0119tna Street, 31\u2013343 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1093\/epirev\/mxn001","article-title":"Schizophrenia: A concise overview of incidence, prevalence, and mortality","volume":"30","author":"McGrath","year":"2008","journal-title":"Epidemiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/sj.mp.4001563","article-title":"Phenotype of schizophrenia: A review and formulation","volume":"10","author":"Tamminga","year":"2005","journal-title":"Mol. Psychiatry"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1093\/schbul\/sbn117","article-title":"Gene-environment interactions in schizophrenia: Review of epidemiological findings and future directions","volume":"34","author":"Rutten","year":"2008","journal-title":"Schizophr. Bull."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1146\/annurev.neuro.25.112701.142754","article-title":"Schizophrenia as a disorder of neurodevelopment","volume":"25","author":"Lewis","year":"2002","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.ijdevneu.2010.10.003","article-title":"Childhood onset schizophrenia: Support for a progressive neurodevelopmental disorder","volume":"29","author":"Rapoport","year":"2011","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/978-3-319-53889-1_12","article-title":"DNA methylation in schizophrenia","volume":"978","author":"Pries","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.pnpbp.2017.10.004","article-title":"DNA methylation and antipsychotic treatment mechanisms in schizophrenia: Progress and future directions","volume":"81","author":"Ovenden","year":"2018","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.aninu.2017.08.009","article-title":"Role of methionine on epigenetic modification of DNA methylation and gene expression in animals","volume":"4","author":"Zhang","year":"2018","journal-title":"Anim. Nutr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1038\/nature05913","article-title":"Perceptions of epigenetics","volume":"447","author":"Bird","year":"2007","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"17095","DOI":"10.1073\/pnas.262658999","article-title":"An epigenetic mouse model for molecular and behavioral neuropathologies related to schizophrenia vulnerability","volume":"99","author":"Tremolizzo","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/ijnp\/pyv054","article-title":"A methionine-induced animal model of schizophrenia: Face and predictive validity","volume":"18","author":"Wang","year":"2015","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"15763","DOI":"10.1074\/jbc.M511767200","article-title":"Evidence that DNA (cytosine-5) methyltransferase regulates synaptic plasticity in the hippocampus","volume":"281","author":"Levenson","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1038\/nn.2666","article-title":"DNA methylation and memory formation","volume":"13","author":"Day","year":"2010","journal-title":"Nat. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1038\/mp.2009.138","article-title":"Brain weight in males is correlated with DNA methylation at IGF2","volume":"15","author":"Pidsley","year":"2010","journal-title":"Mol. Psychiatry"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1177\/1073858415579635","article-title":"DNA methylation in memory formation: Emerging insights","volume":"21","author":"Heyward","year":"2015","journal-title":"Neuroscientist"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.conb.2009.05.001","article-title":"Redox dysregulation, neurodevelopment, and schizophrenia","volume":"19","author":"Do","year":"2009","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1038\/mp.2017.47","article-title":"Oxidative stress-driven parvalbumin interneuron impairment as a common mechanism in models of schizophrenia","volume":"22","author":"Steullet","year":"2017","journal-title":"Mol. Psychiatry"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2547","DOI":"10.1523\/JNEUROSCI.3857-09.2010","article-title":"Redox dysregulation affects the ventral but not dorsal hippocampus: Impairment of parvalbumin neurons, gamma oscillations, and related behaviors","volume":"30","author":"Steullet","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1016\/j.neubiorev.2010.10.008","article-title":"Oxidative stress in schizophrenia: An integrated approach","volume":"35","author":"Bitanihirwe","year":"2011","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2011","DOI":"10.1089\/ars.2010.3603","article-title":"Antioxidants, redox signaling, and pathophysiology in schizophrenia: An integrative view","volume":"15","author":"Yao","year":"2011","journal-title":"Antioxid. Redox. Signal."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Dietrich-Muszalska, A., Chauhan, V., and Grignon, S. (2015). Dysregulation of glutathione synthesis in psychiatric disorders. Studies on Psychiatric disorders. Oxidative Stress in Applied Basic Research and Clinical Practice, Springer. [1st ed.].","DOI":"10.1007\/978-1-4939-0440-2"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1089\/ars.2006.8.1865","article-title":"Redefining oxidative stress","volume":"8","author":"Jones","year":"2006","journal-title":"Antioxid. Redox. Signal."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"C849","DOI":"10.1152\/ajpcell.00283.2008","article-title":"Radical-free biology of oxidative stress","volume":"295","author":"Jones","year":"2008","journal-title":"Am. J. Physiol. Cell. Physiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3721","DOI":"10.1046\/j.1460-9568.2000.00229.x","article-title":"Schizophrenia: Glutathione deficit in cerebrospinal fluid and prefrontal cortex in vivo","volume":"12","author":"Do","year":"2000","journal-title":"Eur. J. Neurosci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1089\/ars.2010.3453","article-title":"Magnetic resonance spectroscopy study of the antioxidant defense system in schizophrenia","volume":"15","author":"Matsuzawa","year":"2011","journal-title":"Antioxid. Redox. Signal."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1155\/2006\/248387","article-title":"Altered glutathione redox state in schizophrenia","volume":"22","author":"Yao","year":"2006","journal-title":"Dis. Markers"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1017\/S1461145710000805","article-title":"Decreased levels of glutathione, the major brain antioxidant, in post-mortem prefrontal cortex from patients with psychiatric disorders","volume":"14","author":"Gawryluk","year":"2011","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1086\/507566","article-title":"Schizophrenia and oxidative stress: Glutamate cysteine ligase modifier as a susceptibility gene","volume":"79","author":"Tosic","year":"2006","journal-title":"Am. J. Hum. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"16621","DOI":"10.1073\/pnas.0706778104","article-title":"Impaired glutathione synthesis in schizophrenia: Convergent genetic and functional evidence","volume":"104","author":"Gysin","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1089\/ars.2010.3463","article-title":"Genetic dysregulation of glutathione synthesis predicts alteration of plasma thiol redox status in schizophrenia","volume":"15","author":"Gysin","year":"2011","journal-title":"Antioxid. Redox. Signal."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3143","DOI":"10.1016\/j.bbagen.2012.09.008","article-title":"Glutathione synthesis","volume":"1830","author":"Lu","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Matsuzawa, D., Obata, T., Shirayama, Y., Nonaka, H., Kanazawa, Y., Yoshitome, E., Takanashi, J., Matsuda, T., Shimizu, E., and Ikehira, H. (2008). Negative correlation between brain glutathione level and negative symptoms in schizophrenia: A 3T 1H-MRS study. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0001944"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1111\/j.1753-4887.1992.tb01298.x","article-title":"Buthionine sulfoximine, an experimental tool to induce glutathione deficiency: Elucidation of glutathione and ascorbate in their role as antioxidants","volume":"50","author":"Broquist","year":"1992","journal-title":"Nutr. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/0024-3205(89)90266-X","article-title":"Methods for depleting brain glutathione","volume":"44","author":"Masukawa","year":"1989","journal-title":"Life Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"49446","DOI":"10.1074\/jbc.M209372200","article-title":"Initial characterization of the glutamate-cysteine ligase modifier subunit Gclm(-\/-) knockout mouse. Novel model system for a severely compromised oxidative stress response","volume":"277","author":"Yang","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1006\/bbrc.2000.3930","article-title":"Knockout of the mouse glutamate cysteine ligase catalytic subunit (Gclc) gene: Embryonic lethal when homozygous, and proposed model for moderate glutathione deficiency when heterozygous","volume":"279","author":"Dalton","year":"2000","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1016\/j.freeradbiomed.2004.06.040","article-title":"Genetically altered mice to evaluate glutathione homeostasis in health and disease","volume":"37","author":"Dalton","year":"2004","journal-title":"Free Radic. Biol. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.bbr.2011.10.020","article-title":"Behavioral phenotyping of glutathione-deficient mice: Relevance to schizophrenia and bipolar disorder","volume":"226","author":"Kulak","year":"2012","journal-title":"Behav. Brain Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1016\/S0891-5849(97)00399-7","article-title":"Spatial learning and memory deficits induced by dopamine administration with decreased glutathione","volume":"24","author":"Erat","year":"1998","journal-title":"Free Radic. Biol. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1002\/1098-2396(20001215)38:4<369::AID-SYN1>3.0.CO;2-Q","article-title":"Synaptic plasticity is impaired in rats with a low glutathione content","volume":"38","author":"Bergado","year":"2000","journal-title":"Synapse"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/S0361-9230(01)00484-1","article-title":"Behavioral and biochemical effects of glutathione depletion in the rat brain","volume":"55","author":"Lorigados","year":"2001","journal-title":"Brain Res. Bull."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/j.neuroscience.2003.11.012","article-title":"An animal model with relevance to schizophrenia: Sex-dependent cognitive deficits in osteogenic disorder-Shionogi rats induced by glutathione synthesis and dopamine uptake inhibition during development","volume":"123","author":"Do","year":"2004","journal-title":"Neuroscience"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.nbd.2003.09.005","article-title":"Low brain glutathione and ascorbic acid associated with dopamine uptake inhibition during rat\u2019s development induce long-term cognitive deficit: Relevance to schizophrenia","volume":"15","author":"Rougemont","year":"2004","journal-title":"Neurobiol. Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1016\/j.nbd.2007.03.001","article-title":"Transitory glutathione deficit during brain development induces cognitive impairment in juvenile and adult rats: Relevance to schizophrenia","volume":"26","author":"Cabungcal","year":"2007","journal-title":"Neurobiol. Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1146\/annurev.bi.52.070183.003431","article-title":"Glutathione","volume":"52","author":"Meister","year":"1983","journal-title":"Annu. Rev. Biochem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1523\/JNEUROSCI.19-02-00562.1999","article-title":"Synthesis of the antioxidant glutathione in neurons: Supply by astrocytes of CysGly as precursor for neuronal glutathione","volume":"19","author":"Dringen","year":"1999","journal-title":"J. Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1515\/CCLM.2007.341","article-title":"Metabolic regulatory properties of S-adenosylmethionine and S-adenosylhomocysteine","volume":"45","author":"Finkelstein","year":"2007","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"35785","DOI":"10.1074\/jbc.M602799200","article-title":"A functional transsulfuration. pathway in the brain links to glutathione homeostasis","volume":"281","author":"Vitvitsky","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"9508","DOI":"10.1016\/S0021-9258(17)42728-1","article-title":"Methionine metabolism in mammals. Distribution of homocysteine between competing pathways","volume":"259","author":"Finkelstein","year":"1984","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1016\/S0021-9258(17)35979-3","article-title":"Methionine metabolism in mammals. Adaptation to methionine excess","volume":"261","author":"Finkelstein","year":"1986","journal-title":"J. Biol. Chem."},{"key":"ref_51","first-page":"209","article-title":"The administration of methionine to chronic schizophrenic patients: A review of ten studies","volume":"8","author":"Cohen","year":"1974","journal-title":"Biol. Psychiatry"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"12578","DOI":"10.1073\/pnas.0505394102","article-title":"Reelin and glutamic acid decarboxylase67 promoter remodeling in an epigenetic methionine-induced mouse model of schizophrenia","volume":"102","author":"Dong","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.biopsych.2004.11.046","article-title":"Valproate corrects the schizophrenia-like epigenetic behavioral modifications induced by methionine in mice","volume":"57","author":"Tremolizzo","year":"2005","journal-title":"Biol. Psychiatry"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.ymgme.2014.10.006","article-title":"Homocysteine and DNA methylation: A review of animal and human literature","volume":"113","author":"Mandaviya","year":"2014","journal-title":"Mol. Genet. Metab."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/S0165-3806(96)80016-2","article-title":"Changes in brain glutathione levels during postnatal development in the rat","volume":"94","author":"Nanda","year":"1996","journal-title":"Brain Res. Dev. Brain Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1073\/pnas.80.3.707","article-title":"Transport and direct utilization of gamma-glutamylcyst(e)ine for glutathione synthesis","volume":"80","author":"Anderson","year":"1983","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.neuro.2010.11.008","article-title":"\u03b3-Glutamylcysteine ameliorates oxidative injury in neurons and astrocytes in vitro and increases brain glutathione in vivo","volume":"32","author":"Le","year":"2011","journal-title":"Neurotoxicology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1046\/j.1471-4159.1997.69020868.x","article-title":"Use of dipeptides for the synthesis of glutathione by astroglia-rich primary cultures","volume":"69","author":"Dringen","year":"1997","journal-title":"J. Neurochem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/0006-2952(90)90503-D","article-title":"Glutathione-degrading capacities of liver and kidney in different species","volume":"40","author":"Hinchman","year":"1990","journal-title":"Biochem. Pharmacol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"501","DOI":"10.18388\/abp.2002_3809","article-title":"The \u03b3-glutamyltransferase activity and non-protein sulfhydryl compounds levels in rat kidney of different age groups","volume":"49","year":"2002","journal-title":"Acta Biochim. Pol."},{"key":"ref_61","first-page":"R348","article-title":"Divergent effects of intravenous GSH and cysteine on renal and hepatic GSH","volume":"263","author":"Aebi","year":"1992","journal-title":"Am. J. Physiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1248\/bpb.17.1535","article-title":"Tissue and subcellular distribution of bound and acid-labile sulfur, and the enzymic capacity for sulfide production in the rat","volume":"17","author":"Ogasawara","year":"1994","journal-title":"Biol. Pharm. Bull."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/0006-2952(92)90121-X","article-title":"Increase in rat brain glutathione following intracerebroventricular administration of gamma-glutamylcysteine","volume":"44","author":"Pileblad","year":"1992","journal-title":"Biochem. Pharmacol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1002\/jnr.10439","article-title":"New model of glutathione deficit during development: Effect on lipid peroxidation in the rat brain","volume":"70","author":"Rougemont","year":"2002","journal-title":"J. Neurosci. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1016\/j.freeradbiomed.2007.06.028","article-title":"Glutathione depletion activates mitogen-activated protein kinase (MAPK) pathways that display organ-specific responses and brain protection in mice","volume":"43","author":"Gonsebatt","year":"2007","journal-title":"Free Radic. Biol. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.neuint.2018.10.007","article-title":"Systemic L-buthionine-S-R-sulfoximine administration modulates glutathione homeostasis via NGF\/TrkA and mTOR signaling in the cerebellum","volume":"121","author":"Petrosyan","year":"2018","journal-title":"Neurochem. Int."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"13005","DOI":"10.1021\/bi001088w","article-title":"The quantitatively important relationship between homocysteine metabolism and glutathione synthesis by the transsulfuration pathway and its regulation by redox changes","volume":"39","author":"Mosharov","year":"2000","journal-title":"Biochemistry"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/0041-008X(91)90208-V","article-title":"Tissue-specific changes in glutathione and cysteine after buthionine sulfoximine treatment of rats and the potential for artifacts in thiol levels resulting from tissue preparation","volume":"107","author":"Standeven","year":"1991","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1093\/jn\/122.8.1693","article-title":"The splanchnic organs, liver and kidney have unique roles in the metabolism of sulfur amino acids and their metabolites in rats","volume":"122","author":"Garcia","year":"1992","journal-title":"J. Nutr."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"364","DOI":"10.3181\/00379727-194-43110","article-title":"Adaptation of adenosylmethionine metabolism and methionine recycling to variations in dietary methionine in the rat","volume":"194","author":"Eloranta","year":"1990","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1146\/annurev.nutr.24.012003.132418","article-title":"Sulfur amino acid metabolism: Pathways for production and removal of homocysteine and cysteine","volume":"24","author":"Stipanuk","year":"2004","journal-title":"Annu. Rev. Nutr."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1652S","DOI":"10.1093\/jn\/136.6.1652S","article-title":"Mammalian cysteine metabolism: New insights into regulation of cysteine metabolism","volume":"136","author":"Stipanuk","year":"2006","journal-title":"J. Nutr."},{"key":"ref_73","first-page":"528","article-title":"Inhibition of glutathione synthesis in the liver leads to S-adenosyl-L-methionine synthetase reduction","volume":"14","author":"Corrales","year":"1991","journal-title":"Hepatology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1006\/bbrc.1998.9232","article-title":"Dopamine formation from tyramine by CYP2D6","volume":"246","author":"Hiroi","year":"1998","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_75","first-page":"593","article-title":"Catechol-O-methyltransferase (COMT): Biochemistry, molecular biology, pharmacology, and clinical efficacy of the new selective COMT inhibitors","volume":"51","author":"Kaakkola","year":"1999","journal-title":"Pharmacol. Rev."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.gene.2013.08.025","article-title":"Neurologically normal development of a patient with severe methionine adenosyltransferase I\/III deficiency after continuing dietary methionine restriction","volume":"530","author":"Hirabayashi","year":"2013","journal-title":"Gene"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.ymgme.2013.08.003","article-title":"Clinical and metabolic findings in patients with methionine adenosyltransferase I\/III deficiency detected by newborn screening","volume":"110","author":"Couce","year":"2013","journal-title":"Mol. Genet. Metab."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1038\/sj.mp.4001337","article-title":"Abnormalities of myelination in schizophrenia detected in vivo with MRI, and post-mortem with analysis of oligodendrocyte protein","volume":"8","author":"Flynn","year":"2003","journal-title":"Mol. Psychiatry"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.biopsych.2013.03.003","article-title":"Myelin and axon abnormalities in schizophrenia measured with magnetic resonance imaging techniques","volume":"74","author":"Du","year":"2013","journal-title":"Biol. Psychiatry"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1097\/YCO.0b013e32835d9e6a","article-title":"Review of functional and anatomical brain connectivity findings in schizophrenia","volume":"26","author":"Fitzsimmons","year":"2013","journal-title":"Curr. Opin. Psychiatry"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.conb.2012.11.004","article-title":"Dysconnectivity, large-scale networks and neuronal dynamics in schizophrenia","volume":"23","author":"Uhlhaas","year":"2013","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1007\/s00726-011-0861-y","article-title":"Modulation of neuronal glutathione synthesis by EAAC1 and its interacting protein GTRAP3-18","volume":"42","author":"Aoyama","year":"2012","journal-title":"Amino Acids"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/s00726-011-0864-8","article-title":"The transsulfuration pathway: A source of cysteine for glutathione in astrocytes","volume":"42","author":"McBean","year":"2012","journal-title":"Amino Acids"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1089\/ars.2011.4391","article-title":"The cystine\/glutamate antiporter system xc\u2212 in health and disease: From molecular mechanisms to novel therapeutic opportunities","volume":"18","author":"Lewerenz","year":"2013","journal-title":"Antioxid. Redox Signal."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1002\/glia.23011","article-title":"Cystine\/glutamate antiporter blockage induces myelin degeneration","volume":"64","author":"Soria","year":"2016","journal-title":"Glia"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0304-3940(01)01810-9","article-title":"Predominant functional activity of the large, neutral amino acid transporter (LAT1) isoform at the cerebrovasculature","volume":"306","author":"Killian","year":"2001","journal-title":"Neurosci. Lett."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"10514","DOI":"10.1523\/JNEUROSCI.3178-06.2006","article-title":"Cystine\/glutamate exchange modulates glutathione supply for neuroprotection from oxidative stress and cell proliferation","volume":"26","author":"Shih","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1002\/glia.21176","article-title":"Regulation of the system x(C)- cystine\/glutamate exchanger by intracellular glutathione levels in rat astrocyte primary cultures","volume":"59","author":"Seib","year":"2011","journal-title":"Glia"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1038\/sj.npp.1301532","article-title":"Contribution of cystine-glutamate antiporters to the psychotomimetic effects of phencyclidine","volume":"33","author":"Baker","year":"2008","journal-title":"Neuropsychopharmacology"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/mp.2011.131","article-title":"Potential metabolite markers of schizophrenia","volume":"18","author":"Yang","year":"2013","journal-title":"Mol. Psychiatry"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.schres.2017.03.041","article-title":"Increased serum levels of cysteine in patients with schizophrenia: A potential marker of cognitive function preservation","volume":"192","author":"Wang","year":"2018","journal-title":"Schizophr. Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.biopsych.2008.03.004","article-title":"N-acetyl cysteine as a glutathione precursor for schizophrenia--a double-blind, randomized, placebo-controlled trial","volume":"64","author":"Berk","year":"2008","journal-title":"Biol. Psychiatry"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Carmeli, C., Knyazeva, M.G., Cu\u00e9nod, M., and Do, K.Q. (2012). Glutathione precursor N-acetyl-cysteine modulates EEG synchronization in schizophrenia patients: A double-blind, randomized, placebo-controlled trial. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0029341"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1097\/WNF.0000000000000001","article-title":"N-acetylcysteine as an adjunct to risperidone for treatment of negative symptoms in patients with chronic schizophrenia: A randomized, double-blind, placebo-controlled study","volume":"36","author":"Farokhnia","year":"2013","journal-title":"Clin. Neuropharmacol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/nature14192","article-title":"Function and information content of DNA methylation","volume":"517","year":"2015","journal-title":"Nature"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1172\/JCI118862","article-title":"Demyelination of the brain is associated with methionine adenosyltransferase I\/III deficiency","volume":"98","author":"Chamberlin","year":"1996","journal-title":"J. Clin. Invest."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"29318","DOI":"10.1074\/jbc.M002725200","article-title":"Increase in plasma homocysteine associated with parallel increases in plasma S-adenosylhomocysteine and lymphocyte DNA hypomethylation","volume":"275","author":"Yi","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Rog\u00f3\u017c, Z., Hereta, M., Kami\u0144ska, K., Le\u015bkiewicz, M., Trojan, E., Lorenc-Koci, E., and Basta-Kaim, A. (2019, January 23\u201327). Glutathione deficit during brain development induces schizophrenia-like symptoms and decreases the brain-derived neurotrophic protein level in the adult Sprague-Dawley rats. Proceedings of the 7th Conference of the Mediterranean Neuroscience Society (MNS), Marrakech, Morrocco.","DOI":"10.26226\/morressier.5d1a037757558b317a1406e3"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pbiomolbio.2015.04.008","article-title":"Epigenetic mechanisms in schizophrenia","volume":"118","author":"Shorter","year":"2015","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1081\/JLC-100103450","article-title":"2-Chloro-1-methylquinolinium tetrafluoroborate as an effective and thiol specific uv-tagging reagent for liquid chromatography","volume":"24","author":"Bald","year":"2001","journal-title":"J. Liq. Chrom. Rel. Technol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1042\/bj1040627","article-title":"A spectrophotometric method for the direct determination of cysteine in the presence of other naturally occurring amino acids","volume":"104","author":"Gaitonde","year":"1967","journal-title":"Biochem. J."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.chroma.2003.11.030","article-title":"Analysis of plasma thiols by high-performance liquid chromatography with ultraviolet detection","volume":"1032","author":"Bald","year":"2004","journal-title":"J. Chromatogr. A"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"3241","DOI":"10.1002\/jssc.201800381","article-title":"Simultaneous determination of total homocysteine, cysteine, glutathione and N-acetylcysteine in brain homogenates by HPLC","volume":"41","author":"Olejarz","year":"2018","journal-title":"J. Sep. Sci."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1016\/j.talanta.2016.09.039","article-title":"Simultaneous determination of methionine and homocysteine by on-column derivatization with o-phtaldialdehyde","volume":"161","author":"Borowczyk","year":"2016","journal-title":"Talanta"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Wnuk, A., Rzemieniec, J., Staro\u0144, J., Litwa, E., Laso\u0144, W., Bojarski, A., and Kajta, M. (2018). Prenatal exposure to benzophenone-3 impairs autophagy, disrupts RXRs\/PPAR\u03b3 signaling, and alters epigenetic and post-translational statuses in brain neurons. Mol. Neurobiol.","DOI":"10.1007\/s12035-018-1401-5"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.jsbmb.2018.04.016","article-title":"Prenatal exposure to benzophenone-3 (BP-3) induces apoptosis, disrupts estrogen receptor expression and alters the epigenetic status of mouse neurons","volume":"182","author":"Wnuk","year":"2018","journal-title":"J. Steroid. Biochem. Mol. Biol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1016\/j.pharep.2015.04.006","article-title":"The effect of combined treatment with risperidone and antidepressants on the MK-801-induced deficits in the social interaction test in rats","volume":"67","year":"2015","journal-title":"Pharmacol. Rep."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/23\/4253\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:36:40Z","timestamp":1760189800000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/23\/4253"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,22]]},"references-count":107,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["molecules24234253"],"URL":"https:\/\/doi.org\/10.3390\/molecules24234253","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,22]]}}}