{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T14:24:37Z","timestamp":1789050277797,"version":"build-2803163510"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,2,15]],"date-time":"2020-02-15T00:00:00Z","timestamp":1581724800000},"content-version":"am","delay-in-days":365,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2019,2,15]],"date-time":"2019-02-15T00:00:00Z","timestamp":1550188800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005825","name":"National Institute of Food and Agriculture","doi-asserted-by":"publisher","award":["HATCH Project ILLU\u2010538\u2010932"],"award-info":[{"award-number":["HATCH Project ILLU\u2010538\u2010932"]}],"id":[{"id":"10.13039\/100005825","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 MH101145"],"award-info":[{"award-number":["R01 MH101145"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Viral encephalitis increases the risk for developing seizures and epilepsy. Indoleamine 2,3\u2010dioxygenase 1 (Ido1) is induced by inflammatory cytokines and functions to metabolize tryptophan to kynurenine. Kynurenine can be further metabolized to produce kynurenic acid and the <jats:italic>N<\/jats:italic>\u2010methyl\u2010<jats:sc>d<\/jats:sc>\u2010aspartate receptor agonist quinolinic acid (QuinA). In the present study, we sought to determine the role of Ido1 in promoting seizures in an animal model of viral encephalitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>C57<jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>\/6J and Ido1 knockout mice (Ido1\u2010<jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content>) were infected with Theiler's murine encephalomyelitis virus (<jats:styled-content style=\"fixed-case\">TMEV<\/jats:styled-content>). Quantitative real\u2010time polymerase chain reaction was used to evaluate hippocampal expression of proinflammatory cytokines, <jats:italic>Ido1<\/jats:italic>, and viral <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>. Body weights and seizure scores were recorded daily. Elevated zero maze was used to assess differences in behavior, and hippocampal pathology was determined by immunohistochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Infected C57<jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>\/6J mice up\u2010regulated proinflammatory cytokines, <jats:italic>Ido1<\/jats:italic>, and genes encoding the enzymatic cascade responsible for QuinA production in the kynurenine pathway prior to the onset of seizures. Seizure incidence was elevated in Ido1\u2010<jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> compared to C57<jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>\/6J mice. Infection increased locomotor activity in Ido1\u2010<jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> compared to C57<jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>\/6J mice. Furthermore, the occurrence of seizures was associated with hyperexcitability. Neither expression of proinflammatory cytokines nor viral <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> was altered as a result of genotype. Immunohistochemical analysis revealed increased hippocampal pathology in Ido1\u2010<jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Our findings suggest that Ido1 deletion promotes seizures and neuropathogenesis during acute <jats:styled-content style=\"fixed-case\">TMEV<\/jats:styled-content> encephalitis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.14675","type":"journal-article","created":{"date-parts":[[2019,2,16]],"date-time":"2019-02-16T04:00:50Z","timestamp":1550289650000},"page":"626-635","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Indoleamine 2,3\u2010dioxygenase 1 deletion promotes Theiler's virus\u2013induced seizures in C57<scp>BL<\/scp>\/6J mice"],"prefix":"10.1111","volume":"60","author":[{"given":"Michal B.","family":"Juda","sequence":"first","affiliation":[{"name":"Department of Animal Sciences 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