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https://www.readbyqxmd.com/read/28214871/restraint-stress-during-pregnancy-rapidly-raises-kynurenic-acid-levels-in-mouse-placenta-and-fetal-brain
#1
Francesca M Notarangelo, Robert Schwarcz
Stressful events during pregnancy adversely affect brain development and may increase the risk of psychiatric disorders later in life. Early changes in the kynurenine (KYN) pathway (KP) of tryptophan (TRP) degradation, which contains several neuroactive metabolites, including kynurenic acid (KYNA), 3-hydroxykynurenine (3-HK), and quinolinic acid (QUIN), may constitute a molecular link between prenatal stress and delayed pathological consequences. To begin testing this hypothesis experimentally, we examined the effects of a 2-h restraint stress on KP metabolism in pregnant FVB/N mice on gestational day 17...
February 18, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28195169/untargeted-metabolomics-of-colonic-digests-reveals-kynurenine-pathway-metabolites-dityrosine-and-3-dehydroxycarnitine-as-red-versus-white-meat-discriminating-metabolites
#2
Caroline Rombouts, Lieselot Y Hemeryck, Thomas Van Hecke, Stefaan De Smet, Winnok H De Vos, Lynn Vanhaecke
Epidemiological research has demonstrated that the consumption of red meat is an important risk factor for the development of colorectal cancer (CRC), diabetes mellitus and cardiovascular diseases. However, there is no holistic insight in the (by-) products of meat digestion that may contribute to disease development. To address this hiatus, an untargeted mass spectrometry (MS)-based metabolomics approach was used to create red versus white meat associated metabolic fingerprints following in vitro colonic digestion using the fecal inocula of ten healthy volunteers...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28187857/adaptive-and-behavioral-changes-in-kynurenine-3-monooxygenase-knockout-mice-relevance-to-psychotic-disorders
#3
Sophie Erhardt, Ana Pocivavsek, Mariaelena Repici, Xi-Cong Liu, Sophie Imbeault, Daniel C Maddison, Marian A R Thomas, Joshua L Smalley, Markus K Larsson, Paul J Muchowski, Flaviano Giorgini, Robert Schwarcz
BACKGROUND: Kynurenine 3-monooxygenase converts kynurenine to 3-hydroxykynurenine, and its inhibition shunts the kynurenine pathway-which is implicated as dysfunctional in various psychiatric disorders-toward enhanced synthesis of kynurenic acid, an antagonist of both α7 nicotinic acetylcholine and N-methyl-D-aspartate receptors. Possibly as a result of reduced kynurenine 3-monooxygenase activity, elevated central nervous system levels of kynurenic acid have been found in patients with psychotic disorders, including schizophrenia...
December 16, 2016: Biological Psychiatry
https://www.readbyqxmd.com/read/28187219/kynurenic-acid-in-schizophrenia-a-systematic-review-and-meta-analysis
#4
Eric Plitman, Yusuke Iwata, Fernando Caravaggio, Shinichiro Nakajima, Jun Ku Chung, Philip Gerretsen, Julia Kim, Hiroyoshi Takeuchi, M Mallar Chakravarty, Gary Remington, Ariel Graff-Guerrero
No abstract text is available yet for this article.
February 10, 2017: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/28181189/deficit-but-not-nondeficit-schizophrenia-is-characterized-by-mucosa-associated-activation-of-the-tryptophan-catabolite-trycat-pathway-with-highly-specific-increases-in-iga-responses-directed-to-picolinic-xanthurenic-and-quinolinic-acid
#5
Buranee Kanchanatawan, Sunee Sirivichayakul, Kiat Ruxrungtham, André F Carvalho, Michel Geffard, Heidi Ormstad, George Anderson, Michael Maes
Evidence suggests that activation of the tryptophan catabolite (TRYCAT) pathway is involved in the pathophysiology of schizophrenia. However, no previous study examined whether TRYCAT pathway activation is associated with deficit schizophrenia. We measured IgA responses to TRYCATs, namely quinolinic acid, picolinic acid, kynurenic acid, xanthurenic acid, and anthranilic acid and 3-OH-kynurenine, in 40 healthy controls and in schizophrenic patients with (n = 40) and without (n = 40) deficit, defined according to the Schedule for the Deficit Syndrome (SDS)...
February 8, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28179491/increases-in-plasma-tryptophan-are-inversely-associated-with-incident-cardiovascular-disease-in-the-prevenci%C3%A3-n-con-dieta-mediterr%C3%A3-nea-predimed-study
#6
Edward Yu, Miguel Ruiz-Canela, Marta Guasch-Ferré, Yan Zheng, Estefania Toledo, Clary B Clish, Jordi Salas-Salvadó, Liming Liang, Dong D Wang, Dolores Corella, Montse Fitó, Enrique Gómez-Gracia, José Lapetra, Ramón Estruch, Emilio Ros, Montserrat Cofán, Fernando Arós, Dora Romaguera, Lluis Serra-Majem, Jose V Sorlí, Frank B Hu, Miguel A Martinez-Gonzalez
Background: During development of cardiovascular disease (CVD), interferon-γ-mediated inflammation accelerates degradation of tryptophan into downstream metabolites. A Mediterranean diet (MedDiet) consisting of a high intake of extra-virgin olive oil (EVOO), nuts, fruits, vegetables, and cereals has been demonstrated to lower the risk of CVD. The longitudinal relation between tryptophan and its downstream metabolites and CVD in the context of a MedDiet is unstudied.Objective: We sought to investigate the relation between metabolites in the tryptophan-kynurenine pathway and CVD in the context of a MedDiet pattern...
February 8, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28173996/perifornical-hypothalamic-pathway-to-the-adrenal-gland-role-for-glutamatergic-transmission-in-the-glucose-counter-regulatory-response
#7
A Sabetghadam, W S Korim, A J M Verberne
Adrenaline is an important counter-regulatory hormone that helps restore glucose homeostasis during hypoglycaemia. However, the neurocircuitry that connects the brain glucose sensors and the adrenal sympathetic outflow to the chromaffin cells is poorly understood. We used electrical microstimulation of the perifornical hypothalamus (PeH) and the rostral ventrolateral medulla (RVLM) combined with adrenal sympathetic nerve activity (ASNA) recording to examine the relationship between the RVLM, the PeH and ASNA...
February 2, 2017: Autonomic Neuroscience: Basic & Clinical
https://www.readbyqxmd.com/read/28163204/overexpression-of-kynurenic-acid-in-stroke-an-endogenous-neuroprotector
#8
A Mangas, J Yajeya, N González, I Ruiz, S Duleu, M Geffard, R Coveñas
It is known that kynurenic acid (KYNA) exerts a neuroprotective effect against the neuronal loss induced by ischemia; acting as a scavenger, and exerting antioxidant action. In order to study the distribution of KYNA, a highly specific monoclonal antibody directed against KYNA was developed. This distribution was studied in control rats and in animals in which a middle cerebral artery occlusion (stroke model) was induced. By double immunohistochemistry, astrocytes containing KYNA and GFAP were exclusively found in the ipsilateral cerebral cortex and/or striatum, at 2, 5 and 21days after the induction of stroke...
February 3, 2017: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
https://www.readbyqxmd.com/read/28155867/kynurenine-pathway-metabolomics-predicts-and-provides-mechanistic-insight-into-multiple-sclerosis-progression
#9
Chai K Lim, Ayse Bilgin, David B Lovejoy, Vanessa Tan, Sonia Bustamante, Bruce V Taylor, Alban Bessede, Bruce J Brew, Gilles J Guillemin
Activation of the kynurenine pathway (KP) of tryptophan metabolism results from chronic inflammation and is known to exacerbate progression of neurodegenerative disease. To gain insights into the links between inflammation, the KP and multiple sclerosis (MS) pathogenesis, we investigated the KP metabolomics profile of MS patients. Most significantly, we found aberrant levels of two key KP metabolites, kynurenic acid (KA) and quinolinic acid (QA). The balance between these metabolites is important as it determines overall excitotoxic activity at the N-methyl-D-Aspartate (NMDA) receptor...
February 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28139681/attenuating-nicotine-reinforcement-and-relapse-by-enhancing-endogenous-brain-levels-of-kynurenic-acid-in-rats-and-squirrel-monkeys
#10
Maria E Secci, Alessia Auber, Leigh V Panlilio, Godfrey H Redhi, Eric B Thorndike, Charles W Schindler, Robert Schwarcz, Steven R Goldberg, Zuzana Justinova
Currently-available antismoking medications have limited efficacy and often fail to prevent relapse. Thus, there is a pressing need for newer, more effective treatment strategies. Recently, we demonstrated that enhancing endogenous levels of kynurenic acid (KYNA, a neuroinhibitory product of tryptophan metabolism) counteracts the rewarding effects of cannabinoids by acting as a negative allosteric modulator of α7 nicotinic receptors (α7nAChRs). Since the effects of KYNA on cannabinoid reward involve nicotinic receptors, in the present study we used rat and squirrel monkey models of reward and relapse to examine the possibility that enhancing KYNA can counteract the effects of nicotine...
January 31, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28053504/nitroglycerin-enhances-the-propagation-of-cortical-spreading-depression-comparative-studies-with-sumatriptan-and-novel-kynurenic-acid-analogues
#11
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
#12
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
#13
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...
February 2017: 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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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