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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.
Front Biosci (Landmark Ed)
January 2025
HUN-REN-SZTE Neuroscience Research Group, Hungarian Research Network, University of Szeged (HUN-REN-SZTE), Danube Neuroscience Research Laboratory, H-6725 Szeged, Hungary.
Backgrounds: Memory and emotion are especially vulnerable to psychiatric disorders such as post-traumatic stress disorder (PTSD), which is linked to disruptions in serotonin (5-HT) metabolism. Over 90% of the 5-HT precursor tryptophan (Trp) is metabolized via the Trp-kynurenine (KYN) metabolic pathway, which generates a variety of bioactive molecules. Dysregulation of KYN metabolism, particularly low levels of kynurenic acid (KYNA), appears to be linked to neuropsychiatric disorders.
View Article and Find Full Text PDFSalt-Responsive Gut Microbiota Induces Sex-Specific Blood Pressure Changes.
Circ Res
December 2024
Department of Physiology and Pharmacology, Microbiome Consortium, Center for Hypertension and Precision Medicine, University of Toledo College of Medicine and Life Sciences, OH (P.B., X.M., N.K.L., B.M., R.T., S.A., I.M., H.H., T.A.J., R.R.A., J.K., B.J., T.Y.).
Background: Tryptophan metabolism is important in blood pressure regulation. The tryptophan-indole pathway is exclusively mediated by the gut microbiota. ACE2 (angiotensin-converting enzyme 2) participates in tryptophan absorption, and a lack of ACE2 leads to changes in the gut microbiota.
View Article and Find Full Text PDFMolecular Insights into the Interaction of Tryptophan Metabolites with the Human Aryl Hydrocarbon Receptor : Tryptophan as Antagonist and no Direct Involvement of Kynurenine.
Front Biosci (Landmark Ed)
September 2024
Pharmacy and Allied Health Sciences, Iqra University, 7580 Karachi, Pakistan.
Background: A direct link between the tryptophan (Trp) metabolite kynurenine (Kyn) and the aryl hydrocarbon receptor (AhR) is not supported by metabolic considerations and by studies demonstrating the failure of Kyn concentrations of up to 100 μM to activate the receptor in cell culture systems using the proxy system of cytochrome 450-dependent metabolism. The Kyn metabolite kynurenic acid (KA) activates the AhR and may mediate the Kyn link. Recent studies demonstrated down regulation and antagonism of activation of the AhR by Trp.
View Article and Find Full Text PDFHarnessing intestinal tryptophan catabolism to relieve atherosclerosis in mice.
Nat Commun
July 2024
Université Paris Cité, Inserm, PARCC, F-75015, Paris, France.
Article Synopsis
- * A high-fat diet (HFD) changes how Trp is processed in the body and can lead to inflammation, which might worsen heart problems.
- * This study shows that controlling Tryptophan metabolism could help reduce gut inflammation and heart disease, leading to new treatment options.
Kidney dysfunction often leads to neurological impairment, yet the complex kidney-brain relationship remains elusive. We employed spatial and bulk metabolomics to investigate a mouse model of rapid kidney failure induced by mouse double minute 2 ( conditional deletion in the kidney tubules to interrogate kidney and brain metabolism. Pathway enrichment analysis of focused plasma metabolomics panel pinpointed tryptophan metabolism as the most altered pathway with kidney failure.
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