Oxidative and Excitatory Neurotoxic Stresses in CRISPR/Cas9-Induced Kynurenine Aminotransferase Knockout Mice: A Novel Model for Despair-Based Depression and Post-Traumatic Stress Disorder

Frontiers in Bioscience-Landmark, Journal Year: 2025, Volume and Issue: 30(1)

Published: Jan. 20, 2025

Backgrounds: Memory and emotion are especially vulnerable to psychiatric disorders such as post-traumatic stress disorder (PTSD), which is linked disruptions in serotonin (5-HT) metabolism. Over 90% of the 5-HT precursor tryptophan (Trp) metabolized via Trp-kynurenine (KYN) metabolic pathway, generates a variety bioactive molecules. Dysregulation KYN metabolism, particularly low levels kynurenic acid (KYNA), appears be neuropsychiatric disorders. The majority KYNA produced by aadat (kat2) gene-encoded mitochondrial kynurenine aminotransferase (KAT) isotype 2. Little known about consequences deleting enzyme gene. Methods: In CRISPR/Cas9-induced knockout (kat2-/-) mice, we examined effects on emotion, memory, motor function, Trp its metabolite levels, activities plasma urine 8-week-old males compared wild-type mice. Results: Transgenic mice showed more depressive-like behaviors forced swim test, but not tail suspension, anxiety, or memory tests. They also had fewer center field corner entries, shorter walking distances, jumping counts open test. Plasma generally consistent with those urine: antioxidant KYNs, 5-hydroxyindoleacetic acid, indole-3-acetic were lower; KATs, kynureninase, monoamine oxidase/aldehyde dehydrogenase lower, 3-monooxygenase was higher; oxidative excitotoxicity indices higher. displayed depression-like behavior learned helplessness model, emotional indifference, deficits, coupled decrease KYNA, shift metabolism toward KYN-3-hydroxykynurenine partial gut microbial Trp-indole pathway metabolite. Conclusions: This first evidence that gene induces uniquely experiences despair, appear associated excitatory neurotoxic stresses. may lead development double-hit preclinical model despair-based depression, better understanding these complex conditions, effective therapeutic strategies elucidating relationship between PTSD pathogenesis.

Language: Английский

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Exercise-induced adaptations in the kynurenine pathway: implications for health and disease management

Frontiers in Sports and Active Living, Journal Year: 2025, Volume and Issue: 7

Published: March 6, 2025

Background Tryptophan (TRP) metabolism through the kynurenine (KYN) pathway is influenced by inflammatory mediators, generating metabolites that regulate immune and responses. Exercise has been proposed as a modulator of this pathway, but its role in health benefits chronic disease management remains unclear. Objective This systematic review examines exercise-induced adaptations KYN their potential implications for management. Additionally, we identify key methodological considerations future research. Methods A structured search PubMed/Medline, Web Science, Scopus was conducted up to October 2024 clinical trials investigating effects exercise training on pathway. Results Of 2,795 articles initially found, 13 involving 592 participants met inclusion criteria. Most studies reported particularly cancer survivors. These appeared be intensity duration. However, several limitations were noted, no included patients with metabolic or cardiovascular diseases. Conclusions Here, show modulates both healthy diseased populations, highlighting prevention further randomized-controlled are needed clarify mechanisms applications, Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/view/CRD42022351481 , PROSPERO (CRD42022351481).

Language: Английский

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Shenqi granules enhance recovery from cerebral ischemia-reperfusion injury by modulating tryptophan and tyrosine metabolism and activating NFE2L2/NRF2

Phytomedicine, Journal Year: 2025, Volume and Issue: 140, P. 156623 - 156623

Published: March 10, 2025

Language: Английский

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Parabacteroides johnsonii Inhibits the Onset and Progression of Colorectal Cancer by Modulating the Gut Microbiota

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: April 7, 2025

Background Colorectal cancer (CRC) is the third most prevalent malignant tumor and second leading cause of cancer-related deaths globally. The genus Parabacteroides an important component gut microbiota. P. distasonis goldsteinii are reported probiotics, their roles in CRC have been investigated related studies. However, association between johnsonii remains unknown. Methods (10–42) Lactococcus formosensis (22–2) were isolated from healthy human feces. 25 mice that demonstrated normal feeding activity randomly assigned to four groups : control (NC group), model (IC (PJ L. (LO group). Colonic tissues IC, PJ, LO colon NC group then collected for HE staining immunohistochemical staining. Fecal samples during hyperproliferative adenoma phases Metagenomic sequencing metabolite analysis. Results intervention reduced number slowed growth colonic tumors, improved histological scores, decreased microenvironmental inflammation levels. composition intestinal flora with cancer, increased microbial species diversity, maintained microbiota stability. Furthermore, abundance Bifidobacterium pseudolongum Lactobacillus, which play a role ameliorating AOM/DSS-induced dysbiosis. affected metabolic pathways, including amino sugar degradation galactose metabolism, sphingolipid synthesis, acid polyphenol synthesis tryptophan metabolism pathway as primary being affected. Conclusion Our study profiled administration reduces tumors lower staging by modulating its metabolites at early stages.

Language: Английский

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Gut microbiota and the tryptophan-kynurenine pathway in anxiety: new insights and treatment strategies

Journal of Neural Transmission, Journal Year: 2025, Volume and Issue: unknown

Published: May 14, 2025

Language: Английский

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