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To provide insight into the physiological role of IDO2 in the brain, behavioral and neurochemical analyses in\n                    <jats:italic>IDO2<\/jats:italic>\n                    knockout (KO) mice were performed.\n                    <jats:italic>IDO2<\/jats:italic>\n                    KO mice showed stereotyped behavior, restricted interest and social deficits, traits that are associated with behavioral endophenotypes of autism spectrum disorder (ASD). IDO2 was colocalized immunohistochemically with tyrosine\u2010hydroxylase\u2010positive cells in dopaminergic neurons. In the striatum and amygdala of\n                    <jats:italic>IDO2<\/jats:italic>\n                    KO mice, decreased dopamine turnover was associated with increased \u03b1\u2010synuclein level. Correspondingly, levels of downstream dopamine D1 receptor signaling molecules such as brain\u2010derived neurotrophic factor and c\u2010Fos positive proteins were decreased. Furthermore, decreased abundance of ramified\u2010type microglia resulted in increased dendritic spine density in the striatum of\n                    <jats:italic>IDO2<\/jats:italic>\n                    KO mice. Both chemogenetic activation of dopaminergic neurons and treatment with methylphenidate, a dopamine reuptake inhibitor, ameliorated the ASD\u2010like behavior of\n                    <jats:italic>IDO2<\/jats:italic>\n                    KO mice. Sequencing analysis of exon regions in\n                    <jats:italic>IDO2<\/jats:italic>\n                    from 309 ASD samples identified a rare canonical splice site variant in one ASD case. These results suggest that the\n                    <jats:italic>IDO2<\/jats:italic>\n                    gene is, at least in part, a factor closely related to the development of psychiatric disorders.\n                  <\/jats:p>","DOI":"10.1111\/febs.17019","type":"journal-article","created":{"date-parts":[[2023,11,30]],"date-time":"2023-11-30T23:54:16Z","timestamp":1701388456000},"page":"945-964","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Indoleamine 2,3\u2010dioxygenase 2 deficiency associates with\u00a0autism\u2010like behavior via dopaminergic neuronal dysfunction"],"prefix":"10.1111","volume":"291","author":[{"given":"Masaki","family":"Ishikawa","sequence":"first","affiliation":[{"name":"Department of Advanced Diagnostic System Development Fujita Health University Graduate School of Health Sciences  Toyoake 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