{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T01:35:11Z","timestamp":1793756111412,"version":"4.6.1"},"reference-count":62,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2016,10,18]],"date-time":"2016-10-18T00:00:00Z","timestamp":1476748800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,10,18]],"date-time":"2016-10-18T00:00:00Z","timestamp":1476748800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Transl Psychiatry"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The kynurenine pathway of tryptophan metabolism has an important role in mediating the behavioral effects of inflammation, which has implications in understanding neuropsychiatric comorbidity and for the development of novel therapies. Inhibition of the rate-limiting enzyme, indoleamine 2,3-dioxygenase (IDO), prevents the development of many of these inflammation-induced preclinical behaviors. However, dysregulation in the balance of downstream metabolism, where neuroactive kynurenines are generated, is hypothesized to be a functionally important pathogenic feature of inflammation-induced depression. Here we utilized two novel transgenic mouse strains to directly test the hypothesis that neurotoxic kynurenine metabolism causes depressive-like behavior following peripheral immune activation. Wild-type (WT) or kynurenine 3-monooxygenase (KMO)-deficient (KMO\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) mice were administered either lipopolysaccharide (LPS, 0.5\u2009mg\u2009kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    ) or saline intraperitoneally. Depressive-like behavior was measured across multiple domains 24\u2009h after immune challenge. LPS precipitated a robust depressive-like phenotype, but KMO\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice were specifically protected from LPS-induced immobility in the tail suspension test (TST) and reduced spontaneous alternations in the Y-maze. Direct administration of 3-hydroxykynurenine, the metabolic product of KMO, caused a dose-dependent increase in depressive-like behaviors. Mice with targeted deletion of 3-hydroxyanthranilic acid dioxygenase (HAAO), the enzyme that generates quinolinic acid, were similarly challenged with LPS. Similar to KMO\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice, LPS failed to increase immobility during the TST. Whereas kynurenine metabolism was generally increased in behaviorally salient brain regions, a distinct shift toward KMO-dependent kynurenine metabolism occurred in the dorsal hippocampus in response to LPS. Together, these results demonstrate that KMO is a pivotal mediator of hippocampal-dependent depressive-like behaviors induced by peripheral LPS challenge.\n                  <\/jats:p>","DOI":"10.1038\/tp.2016.200","type":"journal-article","created":{"date-parts":[[2016,10,18]],"date-time":"2016-10-18T09:47:52Z","timestamp":1476784072000},"page":"e918-e918","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":168,"title":["Neurotoxic kynurenine metabolism is increased in the dorsal hippocampus and drives distinct depressive behaviors during inflammation"],"prefix":"10.1038","volume":"6","author":[{"given":"J M","family":"Parrott","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Redus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Santana-Coelho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Morales","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J C","family":"O'Connor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,10,18]]},"reference":[{"key":"BFtp2016200_CR1","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.it.2005.11.006","volume":"27","author":"CL Raison","year":"2006","unstructured":"Raison CL, Capuron L, Miller AH . 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He has also received funding from the National Institute of Mental Health (R01MH090127), the National Center for Advancing Translational Studies (UL1TR001120) and the Texas Higher Education Coordinating Board (003659-0010-2013). JMP has received funding from the National Institute of Mental Health (1F31MH102070-01A1). The remaining authors declare no conflicts of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}