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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Overview of the role of vitamins and minerals on the kynurenine pathway in health and disease.
TL;DR: The role of vitamin and mineral activity on the kynurenine pathway, which may have an effect on the proper functioning of the human organism, is demonstrated.
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Kynurenine 3-monooxygenase polymorphisms: relevance for kynurenic acid synthesis in patients with schizophrenia and healthy controls.
Maria Holtze,Peter Saetre,Göran Engberg,Lilly Schwieler,Thomas Werge,Ole A. Andreassen,Håkan Hall,Lars Terenius,Ingrid Agartz,Erik G. Jönsson,Martin Schalling,Sophie Erhardt +11 more
TL;DR: The results suggest that the nonsynonymous KMO SNP rs1053230 influences CSF concentrations of KYNA, an end-metabolite of the kynurenine pathway, and the results are tentative until replication.
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Continuous kynurenine administration during the prenatal period, but not during adolescence, causes learning and memory deficits in adult rats
TL;DR: Collectively, these studies provide evidence that a continuous increase in brain KYNA levels during the late prenatal period, but not during adolescence, induces hippocampus-related cognitive dysfunctions later in life.
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Elevated kynurenine pathway metabolism during neurodevelopment: Implications for brain and behavior.
TL;DR: This review describes the changes in KP metabolism in the brain from gestation until adulthood and illustrates how environmental and genetic factors affect the KP during development and presents new data demonstrating that combining perinatal choline-supplementation with embryonic kynurenine manipulation is effective in attenuating cognitive impairments in adult rat offspring.
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Stress-Induced Increase in Kynurenic Acid as a Potential Biomarker for Patients With Schizophrenia and Distress Intolerance
Joshua Chiappelli,Ana Pocivavsek,Katie L. Nugent,Francesca M. Notarangelo,Peter Kochunov,Laura M. Rowland,Robert Schwarcz,L. Elliot Hong +7 more
TL;DR: This stress response behavior-linked biomarker may aid heterogeneity reduction in schizophrenia and other stress-related psychiatric conditions.
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