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To characterize as\u2010yet\u2010unknown pathophysiologies of schizophrenia, we undertook proteomics analysis of the brain in these strains, and detected elevated levels of Mpst, a hydrogen sulfide (H\n                    <jats:sub>2<\/jats:sub>\n                    S)\/polysulfide\u2010producing enzyme, and greater sulfide deposition in C3H than B6 mice.\n                    <jats:italic>Mpst<\/jats:italic>\n                    \u2010deficient mice exhibited improved PPI with reduced storage sulfide levels, while\n                    <jats:italic>Mpst<\/jats:italic>\n                    \u2010transgenic (Tg) mice showed deteriorated PPI, suggesting that \u201csulfide stress\u201d may be linked to PPI impairment. Analysis of human samples demonstrated that the H\n                    <jats:sub>2<\/jats:sub>\n                    S\/polysulfides production system is upregulated in schizophrenia. Mechanistically, the\n                    <jats:italic>Mpst\u2010<\/jats:italic>\n                    Tg brain revealed dampened energy metabolism, while maternal immune activation model mice showed upregulation of genes for H\n                    <jats:sub>2<\/jats:sub>\n                    S\/polysulfides production along with typical antioxidative genes, partly via epigenetic modifications. These results suggest that inflammatory\/oxidative insults in early brain development result in upregulated H\n                    <jats:sub>2<\/jats:sub>\n                    S\/polysulfides production as an antioxidative response, which in turn cause deficits in bioenergetic processes. Collectively, this study presents a novel aspect of the neurodevelopmental theory for schizophrenia, unraveling a role of excess H\n                    <jats:sub>2<\/jats:sub>\n                    S\/polysulfides production.\n                  <\/jats:p>","DOI":"10.15252\/emmm.201910695","type":"journal-article","created":{"date-parts":[[2019,10,28]],"date-time":"2019-10-28T06:00:19Z","timestamp":1572242419000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Excess hydrogen sulfide and polysulfides production underlies a schizophrenia 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