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Kynurenate

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https://www.readbyqxmd.com/read/28053504/nitroglycerin-enhances-the-propagation-of-cortical-spreading-depression-comparative-studies-with-sumatriptan-and-novel-kynurenic-acid-analogues
#1
Levente Knapp, Bence Szita, Kitti Kocsis, László Vécsei, József Toldi
BACKGROUND: The complex pathophysiology of migraine is not yet clearly understood; therefore, experimental models are essential for the investigation of the processes related to migraine headache, which include cortical spreading depression (CSD) and NO donor-induced neurovascular changes. Data on the assessment of drug efficacy in these models are often limited, which prompted us to investigate a novel combined migraine model in which an effective pharmacon could be more easily identified...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28017129/kynurenine-system-and-multiple-sclerosis-pathomechanism-and-drug-targets-with-an-emphasis-on-laquinimod
#2
Zsófia Majláth, Ádám Annus, László Vécsei
Multiple sclerosis is a common chronic, disabling autoimmune neurological disease affecting mainly young adults. In its pathomechanism, neurodegenerative and acute inflammatory characteristics are both involved. Disease-modifying therapies aim to reduce relapse-rate and slow down the deterioration in neurological functions. The currently available therapies fail to exert neuroprotective effects and most of them are associated with potentially toxic side-effects, therefore, ongoing research aims to develop novel drug candidates to cover these therapeutic gaps...
December 23, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/28006716/biomolecular-aspects-of-depression-a-retrospective-analysis
#3
Brandon N Peacock, David J Scheiderer, Gottfried H Kellermann
OBJECTIVE: The effects of psychological stress, oxidative stress, and chronic low grade inflammation on the neuro-immune connection have been implicated in the pathogenesis of depression. Thus, in the recent past, there has been a growing effort in determining the mechanism of this pathogenesis. While attempting to map out, this mechanism researchers and clinicians have searched for clinically relevant biomarkers for use in the diagnosis and for the assessment of those suffering from depression...
November 10, 2016: Comprehensive Psychiatry
https://www.readbyqxmd.com/read/27919017/effects-of-kynurenic-acid-analogue-1-kyna-a1-in-nitroglycerin-induced-hyperalgesia-targets-and-anti-migraine-mechanisms
#4
Rosaria Greco, Chiara Demartini, Anna Maria Zanaboni, Elisa Redavide, Selena Pampalone, Joseph Toldi, Ferenc Fülöp, Fabio Blandini, Giuseppe Nappi, Giorgio Sandrini, László Vécsei, Cristina Tassorelli
BACKGROUND: Trigeminal sensitization represents a major mechanism underlying migraine attacks and their recurrence. Nitroglycerin (NTG) administration provokes spontaneous migraine-like headaches and in rat, an increased sensitivity to the formalin test. Kynurenic acid (KYNA), an endogenous regulator of glutamate activity and its analogues attenuate NTG-induced neuronal activation in the nucleus trigeminalis caudalis (NTC). The anti-hyperalgesic effect of KYNA analogue 1 (KYNA-A1) was investigated on animal models specific for migraine pain...
November 14, 2016: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/27904735/urinary-metabolomics-of-young-italian-autistic-children-supports-abnormal-tryptophan-and-purine-metabolism
#5
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
#6
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...
January 2017: 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
#7
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
#8
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...
February 2017: 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
#9
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
#10
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
#11
Michele Fornaro, António E Nardi, Domenico De Berardis, Mauro Giovanni 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...
December 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
#12
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), quinolinic (QA) and xanthurenic (XA) acids...
January 2017: 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
#13
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
#14
REVIEW
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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