{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T19:14:07Z","timestamp":1787944447900,"version":"build-2784847793"},"reference-count":216,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research, Development, and Innovation Office","award":["NKFIH K138125"],"award-info":[{"award-number":["NKFIH K138125"]}]},{"name":"SZTE SZAOK-KKA","award":["2022\/5S729"],"award-info":[{"award-number":["2022\/5S729"]}]},{"name":"HUN-REN Hungarian Research Network, the JSPS Joint Research Projects under Bilateral Programs","award":["JPJSBP120203803"],"award-info":[{"award-number":["JPJSBP120203803"]}]},{"name":"JSPS Joint Research Projects under Bilateral Programs","award":["JPJSBP120203803"],"award-info":[{"award-number":["JPJSBP120203803"]}]},{"name":"University of Szeged Open Access Fund","award":["7571"],"award-info":[{"award-number":["7571"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: Cognitive, emotional, and social impairments are pervasive across neuropsychiatric conditions, where alterations in the tryptophan (Trp)\u2013kynurenine pathway and its product kynurenic acid (KYNA) from kynurenine aminotransferases (KATs) have been linked to Alzheimer\u2019s disease, Parkinson\u2019s disease, depression, and post-traumatic stress disorder. In novel CRISPR\/Cas9-engineered KAT II knockout (aadat\u2212\/\u2212 also known as kat2\u2212\/\u2212) mice, we observed despair-linked depression-like behavior with peripheral excitotoxicity and oxidative stress. KAT II\u2019s role and its crosstalk with serotonin, indole-pyruvate, and tyrosine\u2013dopamine remain unclear. It is unknown whether deficits extend to cognitive, emotional, motor, and social domains or whether brain tissues mirror peripheral stress. Objectives: Delineate domain-wide behaviors, brain oxidative\/excitotoxic profiles, and pathway interactions attributable to KAT II. Results: Behavior was unchanged across strains. kat2\u2212\/\u2212 deletion remodeled Trp metabolic pathways: 3-hydroxykynurenine increased, xanthurenic acid decreased, KYNA fell in cortex and hippocampus but rose in striatum, quinaldic acid decreased in cerebellum and brainstem. These region-specific changes indicate metabolic stress across the brain and align with higher oxidative load and signs of excitotoxic pressure. Conclusions: Here, we show that KAT II deletion reshapes regional Trp metabolism and amplifies oxidative and excitotoxic imbalance. Although domain-wide behavioral measures, spanning cognition, sociability, and motor coordination, remained largely unchanged, these neurochemical alterations signify a latent emotional bias rather than overt depressive-like behavior. This work, therefore, refines prior findings by delineating KAT II\u2013linked biochemical vulnerability as a potential substrate for stress-reactive affective dysregulation.<\/jats:p>","DOI":"10.3390\/cells14211711","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T13:47:58Z","timestamp":1762177678000},"page":"1711","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Behavioral Balance in Tryptophan Turmoil: Regional Metabolic Rewiring in Kynurenine Aminotransferase II Knockout Mice"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3435-8866","authenticated-orcid":false,"given":"\u00c1gnes","family":"Szab\u00f3","sequence":"first","affiliation":[{"name":"HUN-REN-SZTE Neuroscience Research Group, Hungarian Research Network, University of Szeged, Danube Neuroscience Research Laboratory, H-6725 Szeged, Hungary"},{"name":"Department of Neurology, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, H-6725 Szeged, Hungary"},{"name":"Doctoral School of Clinical Medicine, University of Szeged, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9166-1212","authenticated-orcid":false,"given":"Zsolt","family":"Galla","sequence":"additional","affiliation":[{"name":"Metabolic and Newborn Screening Laboratory, Department of Pediatrics, Albert Szent-Gy\u00f6rgyi Faculty of Medicine, University of Szeged, H-6725 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0888-9353","authenticated-orcid":false,"given":"Eleon\u00f3ra","family":"Spekker","sequence":"additional","affiliation":[{"name":"HUN-REN-SZTE Neuroscience Research Group, Hungarian Research Network, University of Szeged, Danube Neuroscience Research Laboratory, H-6725 Szeged, Hungary"},{"name":"Competence Center for Drug 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Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinuyo","family":"Ozaki","sequence":"additional","affiliation":[{"name":"Center of Biomedical Research, Research Center for Human Disease Modeling, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromi","family":"Inoue","sequence":"additional","affiliation":[{"name":"Center of Biomedical Research, Research Center for Human Disease Modeling, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayo","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Center of Biomedical Research, Research Center for Human Disease Modeling, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, 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