Impaired Kynurenine Pathway Metabolism in The Prefrontal Cortex of Individuals With Schizophrenia
Korrapati V. Sathyasaikumar,Erin K. Stachowski,Ikwunga Wonodi,Rosalinda C. Roberts,Rosalinda C. Roberts,Arash Rassoulpour,Robert P. McMahon,Robert Schwarcz +7 more
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TLDR
The present results further support the hypothesis that the normalization of cortical KP metabolism may constitute an effective new treatment strategy in SZ.Abstract:
The levels of kynurenic acid (KYNA), an astrocyte-derived metabolite of the branched kynurenine pathway (KP) of tryptophan degradation and antagonist of α7 nicotinic acetylcholine and N-methyl-D-aspartate receptors, are elevated in the prefrontal cortex (PFC) of individuals with schizophrenia (SZ). Because endogenous KYNA modulates extracellular glutamate and acetylcholine levels in the PFC, these increases may be pathophysiologically significant. Using brain tissue from SZ patients and matched controls, we now measured the activity of several KP enzymes (kynurenine 3-monooxygenase [KMO], kynureninase, 3-hydroxyanthranilic acid dioxygenase [3-HAO], quinolinic acid phosphoribosyltransferase [QPRT], and kynurenine aminotransferase II [KAT II]) in the PFC, ie, Brodmann areas (BA) 9 and 10. Compared with controls, the activities of KMO (in BA 9 and 10) and 3-HAO (in BA 9) were significantly reduced in SZ, though there were no significant differences between patients and controls in kynureninase, QPRT, and KAT II. In the same samples, we also confirmed the increase in the tissue levels of KYNA in SZ. As examined in rats treated chronically with the antipsychotic drug risperidone, the observed biochemical changes were not secondary to medication. A persistent reduction in KMO activity may have a particular bearing on pathology because it may signify a shift of KP metabolism toward enhanced KYNA synthesis. The present results further support the hypothesis that the normalization of cortical KP metabolism may constitute an effective new treatment strategy in SZ.read more
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Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders.
TL;DR: In this article, a genome-wide significant single nucleotide polymorphism-by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10-8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability.
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Targeting mGlu Receptors for Optimization of Antipsychotic Activity and Disease-Modifying Effect in Schizophrenia.
Ferdinando Nicoletti,Rosamaria Orlando,Luisa Di Menna,Milena Cannella,Serena Notartomaso,Giada Mascio,Luisa Iacovelli,Francesco Matrisciano,Francesco Fazio,Filippo Caraci,Agata Copani,Agata Copani,Giuseppe Battaglia,Valeria Bruno +13 more
TL;DR: The possibility that selective ligands of individual mGlu receptor subtypes may be effective in controlling the core symptoms of schizophrenia, and, in some cases, may impact mechanisms underlying the progression of the disorder, is discussed.
Journal ArticleDOI
Influence of plasma cytokines on kynurenine and kynurenic acid in schizophrenia.
Joshua Chiappelli,Francesca M. Notarangelo,Ana Pocivavsek,Marian A. R. Thomas,Laura M. Rowland,Robert Schwarcz,L. Elliot Hong +6 more
TL;DR: Plasma levels of the major KP metabolites kynurenine and kynurenic acid (KYNA), as well as four major cytokines, were measured in 106 SZ patients and 104 control participants to test the hypothesis that pro-inflammatory cytokines were significantly related to the KP abnormality.
Journal ArticleDOI
Gut microbiota-derived vitamins - underrated powers of a multipotent ally in psychiatric health and disease.
TL;DR: A review of the role of vitamins in mental health and explore the perspectives and potential of how gut microbiota-derived vitamins could contribute to mental health as discussed by the authors and psychiatric treatment is presented in this paper.
Journal ArticleDOI
Alternative kynurenic acid synthesis routes studied in the rat cerebellum
Tonali Blanco Ayala,Rafael Lugo Huitrón,Liliana Carmona Aparicio,Daniela Ramírez Ortega,Dinora F. González Esquivel,José Pedraza Chaverri,Gonzalo Pérez de la Cruz,Camilo Ríos,Robert Schwarcz,Verónica Pérez de la Cruz +9 more
TL;DR: Results suggest that different mechanisms are involved in KYNA production in the rat cerebellum, and that, specifically, DAAO and ROS can function as alternative routes forKYNA production.
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