Behavioral Balance in Tryptophan Turmoil Regional Metabolic Rewiring in Kynurenine Aminotransferase II Knockout Mice /
Background: Cognitive, emotional, and social impairments are pervasive across neuro-psychiatric conditions, where alterations in the tryptophan (Trp)-kynurenine pathway and its product kynurenic acid (KYNA) from kynurenine aminotransferases (KATs) have been linked to Alzheimer's disease, Parkin...
Elmentve itt :
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| Dokumentumtípus: | Cikk |
| Megjelent: |
2025
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| Sorozat: | CELLS
14 No. 21 |
| Tárgyszavak: | |
| doi: | 10.3390/cells14211711 |
| mtmt: | 36412695 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/38247 |
| Tartalmi kivonat: | Background: Cognitive, emotional, and social impairments are pervasive across neuro-psychiatric conditions, where alterations in the tryptophan (Trp)-kynurenine pathway and its product kynurenic acid (KYNA) from kynurenine aminotransferases (KATs) have been linked to Alzheimer's disease, Parkinson's disease, depression, and post-traumatic stress disorder. In novel CRISPR/Cas9-engineered KAT II knockout (aadat −/− also known as kat2 −/−) mice, we observed despair-linked depression-like behavior with peripheral ex-citotoxicity and oxidative stress. KAT II's role and its crosstalk with serotonin, indole-pyruvate, and tyrosine-dopamine 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 −/− deletion remodeled Trp metabolic pathways: 3-hy-droxykynurenine increased, xanthurenic acid decreased, KYNA fell in cortex and hippo-campus 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 Academic Editors: Korrapati V. Citation: Szabó, Á.; Galla, Z.; Spekker, E.; Martos, D.; Szűcs, M.; Fejes-Szabó, A.; Fehér, Á.; Takeda, K.; Ozaki, K.; Inoue, H.; et al. Behavioral Balance in Tryptophan Turmoil: Regional Metabolic Rewiring in Kynurenine Aminotransferase II Knockout Mice. 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-linked biochemical vulnerability as a potential substrate for stress-reactive affective dysregulation. |
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| Terjedelem/Fizikai jellemzők: | 38 |
| ISSN: | 2073-4409 |