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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Sex-related patterns of the gut-microbiota-brain axis in the neuropsychiatric conditions.
Luana M. Manosso,Jaime Lin,Anelise S. Carlessi,Kelen C.C. Recco,João Quevedo,Cinara L. Gonçalves,Gislaine Z. Réus +6 more
TL;DR: In this article, a narrative review has as a mainly aim to show the points sex-related patterns associated to the gut-microbiota-brain axis in the major depressive disorders, schizophrenia, and developmental disorders, including autism spectrum disorders (ASDs).
Journal ArticleDOI
Neuropathology of Kynurenine Pathway of Tryptophan Metabolism
Abdulkarim Tutakhail,Abdulkarim Tutakhail,Lysiane Boulet,Sarah Khabil,Qand Agha Nazari,Hafiza Hamid,François Coudoré +6 more
TL;DR: The relations, the changes, and the mutual effects of KP with major depressive disorders, bipolar disorders, schizophrenia, Parkinson’'s, and Alzheimer’s disease are discussed.
Journal ArticleDOI
Periodontal Pathogens and Neuropsychiatric Health
Abhishek Wadhawan,Mark A. Reynolds,Hina Makkar,Alison J. Scott,Eileen Potocki,Andrew J. Hoisington,Lisa A. Brenner,Aline Dagdag,Christopher A. Lowry,Yogesh Dwivedi,Teodor T. Postolache +10 more
TL;DR: The association between P. gingivalis and cardiovascular, metabolic, and neuropsychiatric illness, and the molecular mechanisms potentially implicated in immune upregulation as well as downregulation induced by the pathogen are reviewed.
Journal ArticleDOI
Immunometabolic Network Interactions of the Kynurenine Pathway in Cutaneous Malignant Melanoma.
Soudabeh Rad Pour,Hiromasa Morikawa,Narsis A. Kiani,David Gomez-Cabrero,David Gomez-Cabrero,Alistair Hayes,Xiaozhong Zheng,Maria Pernemalm,Janne Lehtiö,Damian J. Mole,Johan Hansson,Johan Hansson,Hanna Eriksson,Hanna Eriksson,Jesper Tegnér,Jesper Tegnér +15 more
TL;DR: In this paper, the authors show that mitogen-activated protein kinase pathway (MAPKIs) treatments are associated with alteration of 3-hydroxykynurenine and 3HAA concentrations and led to higher "CXCL11," and "KLRD1" expression that are involved in T and NK cells activation.
Posted ContentDOI
Sex-Dependent Shared and Non-Shared Genetic Architecture Across Mood and Psychotic Disorders
Gabriëlla A.M. Blokland,Jakob Grove,Chia-Yen Chen,Chia-Yen Chen,Chris Cotsapas,Chris Cotsapas,Stuart A. Tobet,Stuart A. Tobet,Robert Handa,Robert Handa,David St Clair,Todd Lencz,Todd Lencz,Bryan J. Mowry,Bryan J. Mowry,Sathish Periyasamy,Sathish Periyasamy,Murray J. Cairns,Paul A. Tooney,Jing Qin Wu,Brian Kelly,George Kirov,Patrick F. Sullivan,Patrick F. Sullivan,Aiden Corvin,Brien P. Riley,Tõnu Esko,Lili Milani,Erik G. Jönsson,Erik G. Jönsson,Aarno Palotie,Aarno Palotie,Aarno Palotie,Hannelore Ehrenreich,Martin Begemann,Agnes A. Steixner-Kumar,Pak C. Sham,Pak C. Sham,Nakao Iwata,Daniel R. Weinberger,Pablo V. Gejman,Pablo V. Gejman,Alan R. Sanders,Alan R. Sanders,Joseph D. Buxbaum,Dan Rujescu,Dan Rujescu,Ina Giegling,Ina Giegling,Bettina Konte,Annette M. Hartmann,Elvira Bramon,Robin M. Murray,Michele T. Pato,Michele T. Pato,Jimmy Lee,Ingrid Melle,Espen Molden,Roel A. Ophoff,Roel A. Ophoff,Roel A. Ophoff,Andrew McQuillin,Nicholas Bass,Rolf Adolfsson,Anil K. Malhotra,Anil K. Malhotra,Nicholas G. Martin,Nicholas G. Martin,Janice M. Fullerton,Janice M. Fullerton,Philip B. Mitchell,Peter R. Schofield,Peter R. Schofield,Andreas J. Forstner,Andreas J. Forstner,Franziska Degenhardt,Franziska Degenhardt,Sabrina K. Schaupp,Ashley L. Comes,Manolis Kogevinas,Jose Guzman-Parra,Andreas Reif,Fabian Streit,Lea Sirignano,Sven Cichon,Maria Grigoroiu-Serbanescu,Joanna Hauser,Jolanta Lissowska,Fermín Mayoral,Bertram Müller-Myhsok,Bertram Müller-Myhsok,Beata Świątkowska,Thomas G. Schulze,Markus M. Nöthen,Marcella Rietschel,John R. Kelsoe,Marion Leboyer,Marion Leboyer,Stéphane Jamain,Stéphane Jamain,Bruno Etain,Frank Bellivier,John B. Vincent,Martin Alda,Martin Alda,Claire O'Donovan,Pablo Cervantes,Joanna M. Biernacka,Mark A. Frye,Susan L. McElroy,Laura J. Scott,Eli A. Stahl,Eli A. Stahl,Mikael Landén,Mikael Landén,Marian L. Hamshere,Olav B. Smeland,Srdjan Djurovic,Srdjan Djurovic,Arne E. Vaaler,Ole A. Andreassen,Bernhard T. Baune,Bernhard T. Baune,Tracy Air,Martin Preisig,Rudolf Uher,Douglas F. Levinson,Myrna M. Weissman,James B. Potash,Jianxin Shi,James A. Knowles,Roy H. Perlis,Roy H. Perlis,Susanne Lucae,Dorret I. Boomsma,Dorret I. Boomsma,Brenda W.J.H. Penninx,Jouke-Jan Hottenga,Jouke-Jan Hottenga,Eco J. C. de Geus,Eco J. C. de Geus,Gonneke Willemsen,Gonneke Willemsen,Yuri Milaneschi,Henning Tiemeier,Hans J. Grabe,Alexander Teumer,Sandra Van der Auwera,Uwe Völker,Steven P. Hamilton,Patrik K. E. Magnusson,Alexander Viktorin,Divya Mehta,Niamh Mullins,Niamh Mullins,Mark Adams,Gerome Breen,Andrew M. McIntosh,Cathryn M. Lewis,David M. Hougaard,David M. Hougaard,Merete Nordentoft,Merete Nordentoft,Merete Nordentoft,Ole Mors,Ole Mors,Preben Bo Mortensen,Thomas Werge,Thomas Werge,Thomas Werge,Thomas Damm Als,Thomas Damm Als,Anders D. Børglum,Anders D. Børglum,Tracey L. Petryshen,Jordan W. Smoller,Jordan W. Smoller,Jill M. Goldstein +177 more
TL;DR: In the largest genome-wide GxS analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes, but significant sexdependent effects were enriched for genes related to neuronal development, immune and vascular functions across and within SCZ, BIP, and MDD.
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