Research Square (Research Square), Год журнала: 2025, Номер unknown
Опубликована: Апрель 7, 2025
Язык: Английский
Research Square (Research Square), Год журнала: 2025, Номер unknown
Опубликована: Апрель 7, 2025
Язык: Английский
Frontiers in Bioscience-Landmark, Год журнала: 2025, Номер 30(1)
Опубликована: Янв. 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.
Язык: Английский
Процитировано
1Frontiers in Sports and Active Living, Год журнала: 2025, Номер 7
Опубликована: Март 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).
Язык: Английский
Процитировано
0Phytomedicine, Год журнала: 2025, Номер 140, С. 156623 - 156623
Опубликована: Март 10, 2025
Язык: Английский
Процитировано
0Research Square (Research Square), Год журнала: 2025, Номер unknown
Опубликована: Апрель 7, 2025
Язык: Английский
Процитировано
0