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
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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Inflammatory Pathways in Psychiatric Disorders: The case of Schizophrenia and Depression.
TL;DR: There is a large body of compelling evidence on the role of inflammatory pathways in depression and schizophrenia, and most of these findings show their roles in the pathophysiology of the above disorders, although additional studies are warranted to investigate the therapeutic potential of various immune signaling targets discussed.
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Prenatal kynurenine treatment in rats causes schizophrenia-like broad monitoring deficits in adulthood.
TL;DR: The findings suggest a potential etiology of broad monitoring deficits in schizophrenia, which may constitute a core cognitive deficit.
Journal ArticleDOI
The Trace Kynurenine, Cinnabarinic Acid, Displays Potent Antipsychotic-Like Activity in Mice and Its Levels Are Reduced in the Prefrontal Cortex of Individuals Affected by Schizophrenia
Martina Ulivieri,Joanna M. Wierońska,Luana Lionetto,Katiuscia Martinello,Paulina Cieslik,Agnieszka Chocyk,Martina Curto,Martina Curto,Luisa Di Menna,Luisa Iacovelli,Anna Traficante,Francesca Liberatore,Giada Mascio,Nico Antenucci,Giuseppe Giannino,Matteo Vergassola,Anna Pittaluga,Valeria Bruno,Giuseppe Battaglia,Sergio Fucile,Maurizio Simmaco,Ferdinando Nicoletti,Andrzej Pilc,Francesco Fazio +23 more
TL;DR: It is suggested that CA is a potent endogenous antipsychotic-like molecule and reduced CA levels in the PFC might contribute to the pathophysiology of schizophrenia.
Journal ArticleDOI
Kynurenines and the Endocannabinoid System in Schizophrenia: Common Points and Potential Interactions
Ferenc Zádor,Gábor Nagy-Grócz,Gabriella Kekesi,Szabolcs Dvorácskó,Edina Szűcs,Csaba Tömböly,Gyongyi Horvath,Sándor Benyhe,László Vécsei +8 more
TL;DR: The present study focuses on the main common points and potential interactions between kynurenines and the ECS in schizophrenia, which include the regulation of glutamatergic/dopaminergic/γ-aminobutyric acidergic neurotransmission, their presence in astrocytes, and their role in inflammatory mechanisms.
Journal ArticleDOI
Enzymatic transamination of d-kynurenine generates kynurenic acid in rat and human brain
Verónica Pérez de la Cruz,Laura Amori,Korrapati V. Sathyasaikumar,Xiao-Dan Wang,Francesca M. Notarangelo,Hui-Qiu Wu,Robert Schwarcz +6 more
TL;DR: The authors showed that kynurenic acid production from d-kynurenine, like the more efficient kynurnic acid synthesis from l-Kynurenines, is blocked by aminotransferase inhibitor amino-oxyacetic acid.
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