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Kynurenate

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https://www.readbyqxmd.com/read/27904735/urinary-metabolomics-of-young-italian-autistic-children-supports-abnormal-tryptophan-and-purine-metabolism
#1
Federica Gevi, Lello Zolla, Stefano Gabriele, Antonio M Persico
BACKGROUND: Autism spectrum disorder (ASD) is still diagnosed through behavioral observation, due to a lack of laboratory biomarkers, which could greatly aid clinicians in providing earlier and more reliable diagnoses. Metabolomics on human biofluids provides a sensitive tool to identify metabolite profiles potentially usable as biomarkers for ASD. Initial metabolomic studies, analyzing urines and plasma of ASD and control individuals, suggested that autistic patients may share some metabolic abnormalities, despite several inconsistencies stemming from differences in technology, ethnicity, age range, and definition of "control" status...
2016: Molecular Autism
https://www.readbyqxmd.com/read/27886578/kynurenic-acid-and-psychotic-symptoms-and-personality-traits-in-twins-with-psychiatric-morbidity
#2
Magdalena E Kegel, Viktoria Johansson, Lennart Wetterberg, Maria Bhat, Lilly Schwieler, Tyrone D Cannon, Ina Schuppe-Koistinen, Göran Engberg, Mikael Landén, Christina M Hultman, Sophie Erhardt
Increased cytokines and kynurenic acid (KYNA) levels in cerebrospinal fluid (CSF) have been reported in patients with schizophrenia and bipolar disorder. The aim of the present study was to investigate cytokines and kynurenines in the CSF of twin pairs discordant for schizophrenia or bipolar disorder and to study these CSF markers in relation to psychotic symptoms and personality traits. CSF levels of tryptophan (TRP), KYNA, quinolinic acid (QUIN), interleukin (IL)-6, IL-8 and tumor necrosis factor-alpha (TNF-α) were analyzed in 23 twins with schizophrenia or bipolar disorder, and in their not affected co-twins...
November 16, 2016: Psychiatry Research
https://www.readbyqxmd.com/read/27870780/the-activation-of-metabotropic-glutamate-5-receptors-in-the-rat-ventral-tegmental-area-increases-dopamine-extracellular-levels
#3
Carla Ferrada, Ramón Sotomayor-Zárate, Jorge Abarca, Katia Gysling
The mesocorticolimbic circuit projects to the prefrontal cortex, hippocampus, amygdala, and nucleus accumbens, among others, and it originates in the dopaminergic neurons of the ventral tegmental area (VTA). The VTA receives glutamatergic inputs from the prefrontal cortex and several subcortical regions. The glutamate released activates dopaminergic neurons and its action depends on the activation of ionotropic and metabotropic glutamate receptors. VTA dopaminergic neurons release dopamine (DA) from axon terminals in the innervated regions and somatodendritically in the VTA itself...
January 1, 2017: Neuroreport
https://www.readbyqxmd.com/read/27859255/modulation-of-multidrug-resistance-associated-proteins-function-in-erythrocytes-in-glycerol-induced-acute-renal-failure-rats
#4
Aoi Matsushima, Keisuke Oda, Nobuhiro Mori, Teruo Murakami
OBJECTIVES: Evaluation of the function of multidrug resistance-associated proteins (MRPs) expressed in erythrocytes and screening of endogenous MRPs modulator(s) in glycerol-induced acute renal failure (ARF) rats. METHODS: Concentrations of 2,4-dinitrophenyl-S-glutathione (DNP-SG), a substrate for MRPs, in erythrocytes after administration of 1-chloro-2,4-dintrobenzene (CDNB), a precursor of DNP-SG, were determined in control and ARF rats. The screening of endogenous MRPs modulator(s) was performed using washed erythrocytes and inside-out erythrocyte membrane vesicles (IOVs) in vitro...
November 18, 2016: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/27832762/tryptophan-metabolism-its-relation-to-inflammation-and-stress-markers-and-association-with-psychological-and-cognitive-functioning-tasmanian-chronic-kidney-disease-pilot-study
#5
Naama Karu, Charlotte McKercher, David S Nichols, Noel Davies, Robert A Shellie, Emily F Hilder, Matthew D Jose
BACKGROUND: Adults with chronic kidney disease (CKD) exhibit alterations in tryptophan metabolism, mainly via the kynurenine pathway, due to higher enzymatic activity induced mainly by inflammation. Indoles produced by gut-microflora are another group of tryptophan metabolites related to inflammation and conditions accompanying CKD. Disruptions in tryptophan metabolism have been associated with various neurological and psychological disorders. A high proportion of CKD patients self-report symptoms of depression and/or anxiety and decline in cognitive functioning...
November 10, 2016: BMC Nephrology
https://www.readbyqxmd.com/read/27828964/chronic-treatment-with-the-ido1-inhibitor-1-methyl-d-tryptophan-minimizes-the-behavioural-and-biochemical-abnormalities-induced-by-unpredictable-chronic-mild-stress-in-mice-comparison-with-fluoxetine
#6
Anthony Laugeray, Jean-Marie Launay, Jacques Callebert, Oguz Mutlu, Gilles J Guillemin, Catherine Belzung, Pascal R Barone
We demonstrated that confronting mice to the Unpredictable Chronic Mild Stress (UCMS) procedure-a validated model of stress-induced depression-results in behavioural alterations and biochemical changes in the kynurenine pathway (KP), suspected to modify the glutamatergic neurotransmission through the imbalance between downstream metabolites such as 3-hydroxykynurenine, quinolinic and kynurenic acids. We showed that daily treatment with the IDO1 inhibitor 1-methyl-D-tryptophan partially rescues UCMS-induced KP alterations as does the antidepressant fluoxetine...
2016: PloS One
https://www.readbyqxmd.com/read/27802062/experimental-drugs-for-bipolar-psychosis
#7
Michele Fornaro, António E Nardi, Domenico De Berardis, Mauro G Carta
Psychotic features are common in bipolar disorder (BD), especially during acute mania. Even when early detected, their long-term management is difficult, essentially due to the unsatisfactory efficacy/tolerability profile of currently available treatments, thus soliciting the development of novel experimental drugs. Areas covered: Potential drug targets towards the development of experimental drugs in the treatment of bipolar psychosis are yet to be systematically characterized. Among other potential avenues, the kynurenic acid pathway may represent an intriguing opportunity...
November 1, 2016: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/27778340/maternal-protein-restriction-during-gestation-and-lactation-in-the-rat-results-in-increased-brain-levels-of-kynurenine-and-kynurenic-acid-in-their-adult-offspring
#8
Paula Honório de Melo Martimiano, André de Sa Braga Oliveira, Véronique Ferchaud-Roucher, Mikaël Croyal, Audrey Aguesse, Isabelle Grit, Khadija Ouguerram, Sandra Lopes de Souza, Bertrand Kaeffer, Francisco Bolaños-Jiménez
Early malnutrition is a risk factor for depression and schizophrenia. Since the offspring of malnourished dams exhibit increased brain levels of serotonin (5-HT), a tryptophan-derived neurotransmitter involved in the pathophysiology of these mental disorders, it is believed that the deleterious effects of early malnutrition on brain function are due in large part to altered serotoninergic neurotransmission resulting from impaired tryptophan (Trp) metabolism. However, tryptophan is also metabolized through the kynurenine (KYN) pathway yielding several neuroactive compounds including kynurenic (KA), Qinolinic (QA) and Xanthurenic (XA) acids...
October 25, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27756833/the-frontal-cortex-as-a-network-hub-controlling-mood-and-cognition-probing-its-neurochemical-substrates-for-improved-therapy-of-psychiatric-and-neurological-disorders
#9
Mark J Millan, Jean-Michel Rivet, Alain Gobert
The highly-interconnected and neurochemically-rich frontal cortex plays a crucial role in the regulation of mood and cognition, domains disrupted in depression and other central nervous system disorders, and it is an important site of action for their therapeutic control. For improving our understanding of the function and dysfunction of the frontal cortex, and for identifying improved treatments, quantification of extracellular pools of neuromodulators by microdialysis in freely-moving rodents has proven indispensable...
October 17, 2016: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/27755520/-the-kynurenic-acid-hypothesis-a-new-look-at-etiopathogenesis-and-treatment-of-schizophrenia
#10
Marta Flis, Kinga Szymona, Justyna Morylowska-Topolska, Anna Urbańska, Paweł Krukow, Martyna Kandefer-Szerszeń, Barbara Zdzisińska, Ewa M Urbańska, Hanna Karakuła-Juchnowicz
Kynurenic acid (KYNA) is a neuroactive metabolite of tryptophan formed in the brain and in the periphery, known to block ionotropic glutamate receptors and α7 nicotinic receptors, and to act as a ligand of G protein-coupled GPR35 receptors and human aryl hydrocarbon (AHR) receptors. KYNA seems to modulate a number of mechanisms involved in the pathogenesis of schizophrenia including dopaminergic transmission in mesolimbic and mesocortical areas or glutamatemediated neurotransmission. The kynurenine hypothesis of schizophrenia links the occurrence of positive and negative symptoms of schizophrenia and cognitive impairments characteristic for the disease with the disturbances of kynurenine pathway function...
September 29, 2016: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/27746712/n-methyl-d-aspartate-receptor-antagonist-kynurenic-acid-affects-human-cortical-development
#11
Inseyah Bagasrawala, Nada Zecevic, Nevena V Radonjić
Kynurenic acid (KYNA), a neuroactive metabolite of tryptophan degradation, acts as an endogenous N-methyl-D-aspartate receptor (NMDAR) antagonist. Elevated levels of KYNA have been observed in pregnant women after viral infections and are considered to play a role in neurodevelopmental disorders. However, the consequences of KYNA-induced NMDAR blockade in human cortical development still remain elusive. To study the potential impact of KYNA on human neurodevelopment, we used an in vitro system of multipotent cortical progenitors, i...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27738521/kynurenic-acid-an-aryl-hydrocarbon-receptor-ligand-is-elevated-in-serum-of-zucker-fatty-rats
#12
G Oxenkrug, J Cornicelli, M van der Hart, J Roeser, P Summergrad
Obesity is an increasingly urgent global problem and the molecular mechanisms of obesity are not fully understood. Dysregulation of the tryptophan (Trp) - kynurenine (Kyn) metabolic pathway (TKP) have been suggested as a mechanism of obesity and described in obese humans and in animal models of obesity. However, to the best of our knowledge, TKP metabolism has not been studied in leptin-receptor-deficient Zucker fatty rats (ZFR) (fa/fa), the best-known and most widely used rat model of obesity. We were interested to determine if there are any deviations of TKP in ZFR...
2016: Integrative Molecular Medicine
https://www.readbyqxmd.com/read/27708848/metabolomics-identified-metabolites-associated-with-body-mass-index-and-prospective-weight-gain-among-mexican-american-women
#13
H Zhao, J Shen, D Djukovic, C Daniel-MacDougall, H Gu, X Wu, W-H Chow
OBJECTIVE: Obesity is a metabolic disease. However, the underlying molecular mechanisms linking metabolic profiles and weight gain are largely unknown. METHODS: Here, we used semi-targeted metabolomics to assay 156 metabolites selected from 25 key metabolic pathways in plasma samples from 300 non-smoking healthy women identified from Mano-A-Mano, the Mexican American Cohort study. The study subjects were randomly divided into two cohorts: training (N = 200) and testing (N = 100) cohorts...
September 2016: Obesity Science & Practice
https://www.readbyqxmd.com/read/27697587/reversal-of-schizophrenia-like-symptoms-and-immune-alterations-in-mice-by-immunomodulatory-drugs
#14
Tatiane da Silva Araújo, Adriano Jose Maia Chaves Filho, Aline Santos Monte, Ana Isabelle de Góis Queiroz, Rafaela Carneiro Cordeiro, Michel de Jesus Souza Machado, Ricardo de Freitas Lima, David Freitas de Lucena, Michael Maes, Danielle Macêdo
Immune dysregulation observed in schizophrenia alters tryptophan metabolism. Tryptophan metabolism is triggered by indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO). Tryptophan is converted to quinolinic acid, a potent neurotoxin, and to kynurenic acid, an NMDA antagonist. 1-Methyl-D-tryptophan (MDT) inhibits IDO. Melatonin is metabolized by IDO while inhibiting TDO. We evaluated the reversal of ketamine-induced schizophrenia-like behavioral and neurochemical alterations in mice by the administration of MDT (20 or 40 mg/kg, i...
January 2017: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/27693848/kynurenine-3-monooxygenase-is-implicated-in-antidepressants-responsive-depressive-like-behaviors-and-monoaminergic-dysfunctions
#15
Tomoyuki Tashiro, Yuki Murakami, Akihiro Mouri, Yukio Imamura, Toshitaka Nabeshima, Yasuko Yamamoto, Kuniaki Saito
l-Tryptophan (TRP) is metabolized via serotonin and kynurenine pathways (KP). Several studies have demonstrated that abnormality of both pathways is involved in the pathogenesis of major depressive disorder (MDD). Kynurenine 3-monooxygenase (KMO), a pivotal enzyme in the KP, has been suggested to play major roles in physiological and pathological events mediated by bioactive kynurenine metabolites. In this study, we investigated the role of KMO in the emotional and cognitive functions by using KMO knockout (KO) mice...
September 28, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27690267/effect-of-feed-supplementation-with-kynurenic-acid-on-the-morphology-of-the-liver-kidney-and-gills-in-rainbow-trout-oncorhynchus-mykiss-walbaum-1792-healthy-and-experimentally-infected-with-yersinia-ruckeri
#16
E Kaczorek, J Szarek, M Mikiewicz, E Terech-Majewska, P Schulz, J Małaczewska, R Wójcik, A K Siwicki
Kynurenic acid (KYNA) is an endogenous substance produced on the kynurenine pathway which is primarily known for its neuroactive properties. Recently, it has been proven that KYNA is a selective ligand for G protein-coupled receptor (GPR 35), presented on immunocompetent cells such as T lymphocytes. This opens up new possibilities of its application as an immunostimulating substance in aquaculture. Thus far, no histopathological investigations in fish have been completed to evaluate influence of KYNA supplementation in feed...
September 30, 2016: Journal of Fish Diseases
https://www.readbyqxmd.com/read/27686065/a-non-targeted-metabolite-profiling-pilot-study-suggests-that-tryptophan-and-lipid-metabolisms-are-linked-with-adhd-like-behaviours-in-dogs
#17
Jenni Puurunen, Sini Sulkama, Katriina Tiira, Cesar Araujo, Marko Lehtonen, Kati Hanhineva, Hannes Lohi
BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a prevalent and multifactorial neuropsychiatric disorder in the human population worldwide. Complex etiology and clinical heterogeneity have challenged the research, diagnostics and treatment of the disease. Hyperactive and impulsive behaviour has also been observed in dogs, and they could offer a physiologically relevant model for human ADHD. As a part of our ongoing study to understand the molecular etiology of canine anxiety traits, this study was aimed to pilot an approach to identify metabolic biomarkers in canine ADHD-like behaviours for research, diagnostics and treatment purposes...
September 29, 2016: Behavioral and Brain Functions: BBF
https://www.readbyqxmd.com/read/27629500/a-comparative-assessment-of-two-kynurenic-acid-analogs-in-the-formalin-model-of-trigeminal-activation-a-behavioral-immunohistochemical-and-pharmacokinetic-study
#18
Gábor Veres, Annamária Fejes-Szabó, Dénes Zádori, Gábor Nagy-Grócz, Anna M László, Attila Bajtai, István Mándity, Márton Szentirmai, Zsuzsanna Bohár, Klaudia Laborc, István Szatmári, Ferenc Fülöp, László Vécsei, Árpád Párdutz
Kynurenic acid (KYNA) has well-established protective properties against glutamatergic neurotransmission, which plays an essential role in the activation and sensitization process during some primary headache disorders. The goal of this study was to compare the effects of two KYNA analogs, N-(2-N,N-dimethylaminoethyl)-4-oxo-1H-quinoline-2-carboxamide hydrochloride (KA-1) and N-(2-N-pyrrolidinylethyl)-4-oxo-1H-quinoline-2-carboxamide hydrochloride (KA-2), in the orofacial formalin test of trigeminal pain. Following pretreatment with KA-1 or KA-2, rats were injected with subcutaneous formalin solution in the right whisker pad...
September 14, 2016: Journal of Neural Transmission
https://www.readbyqxmd.com/read/27623092/kynurenine-pathway-metabolism-following-prenatal-kmo-inhibition-and-in-mecp2-mice-using-liquid-chromatography-tandem-mass-spectrometry
#19
Caroline M Forrest, Peter G E Kennedy, Jean Rodgers, R Neil Dalton, Charles Turner, L Gail Darlington, Stuart R Cobb, Trevor W Stone
To quantify the full range of tryptophan metabolites along the kynurenine pathway, a liquid chromatography - tandem mass spectrometry method was developed and used to analyse brain extracts of rodents treated with the kynurenine-3-mono-oxygenase (KMO) inhibitor Ro61-8048 during pregnancy. There were significant increases in the levels of kynurenine, kynurenic acid, anthranilic acid and 3-hydroxy-kynurenine (3-HK) in the maternal brain after 5 h but not 24 h, while the embryos exhibited high levels of kynurenine, kynurenic acid and anthranilic acid after 5 h which were maintained at 24 h post-treatment...
September 10, 2016: Neurochemistry International
https://www.readbyqxmd.com/read/27619930/kynurenine-pathway-and-white-matter-microstructure-in-bipolar-disorder
#20
Sara Poletti, Aye Mu Myint, Gregor Schüetze, Irene Bollettini, Elena Mazza, Doris Grillitsch, Clara Locatelli, Markus Schwarz, Cristina Colombo, Francesco Benedetti
Decreased availability of serotonin in the central nervous system has been suggested to be a central factor in the pathogenesis of depression. Activation of indoleamine 2-3 dioxygenase following a pro-inflammatory state could reduce the amount of tryptophan converted to serotonin and increase the production of tryptophan catabolites such as kynurenic acid, an antagonist of ionotropic excitatory aminoacid receptors, whose levels are reduced in bipolar disorder. Abnormalities in white matter (WM) integrity have been widely reported in BD...
September 12, 2016: European Archives of Psychiatry and Clinical Neuroscience
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