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Kynurenate

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https://www.readbyqxmd.com/read/28900168/identification-of-key-metabolic-changes-during-liver-fibrosis-progression-in-rats-using-a-urine-and-serum-metabolomics-approach
#1
Hong Chang, Hong-Yu Meng, Shu-Min Liu, Yu Wang, Xiao-Xu Yang, Fang Lu, Hong-Yu Wang
Reversibility of hepatic fibrosis is an intrinsic response to chronic injury, and with on-going damage, fibrosis can progress to its end-stage consequence, cirrhosis. Non-invasive and reliable biomarkers for early detection of liver fibrosis are needed. Based on the CCl4-induced liver fibrosis rat model, urinary and serum metabolic profiling performed by LC-QTOF-MS associated with histological progression were utilized to identify liver fibrosis-specific potential biomarkers for early prediction and to reveal significant fibrotic pathways and their dynamic changes in different stages of liver fibrosis...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28893581/tryptophan-circuit-in-fatigue-from-blood-to-brain-and-cognition
#2
Masatoshi Yamashita, Takanobu Yamamoto
Brain tryptophan and its neuroactive metabolites play key roles in central fatigue. However, previous brain function analysis targets may have included both glia and neurons together. Here, we clarified the fatigue-cognitive circuit of the central-peripheral linkage, including the role of glial-neuronal interaction in cognition. Using a rat model of central fatigue induced by chronic sleep disorder (CFSD), we isolated presynaptic terminals and oligodendrocytes. Results showed that compared to control group, presynaptic levels of tryptophan, kynurenine, and kynurenic acid, but not serotonin, in the CFSD group were higher in the hypothalamus and hippocampus...
September 8, 2017: Brain Research
https://www.readbyqxmd.com/read/28875464/changes-in-tryptophan-catabolite-trycat-pathway-patterning-are-associated-with-mild-impairments-in-declarative-memory-in-schizophrenia-and-deficits-in-semantic-and-episodic-memory-coupled-with-increased-false-memory-creation-in-deficit-schizophrenia
#3
Buranee Kanchanatawan, Solaphat Hemrungrojn, Supaksorn Thika, Sunee Sirivichayakul, Kiat Ruxrungtham, André F Carvalho, Michel Geffard, George Anderson, Michael Maes
Evidence indicates that schizophrenia and in particular negative symptoms and deficit schizophrenia are accompanied by neurocognitive impairments and changes in the patterning of the tryptophan catabolite (TRYCAT) pathway. This cross-sectional study was carried out to examine the associations between cognitive functions (as measured with Consortium to Establish a Registry for Alzheimer's disease (CERAD)) and TRYCAT pathway patterning in patients with (n = 40) and without (n = 40) deficit schizophrenia and normal controls (n = 40)...
September 5, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28867283/kynurenic-acid-is-reduced-in-females-and-oral-contraceptive-users-implications-for-depression
#4
Timothy B Meier, Wayne C Drevets, T Kent Teague, Brent E Wurfel, Sven C Mueller, Jerzy Bodurka, Robert Dantzer, Jonathan Savitz
The incidence of depression is approximately 2-fold greater in women than men but the biological mechanisms underlying this phenomenon remain unclear. One potential mechanism that has been understudied is immune function, which is modulated by sex hormones and differs considerably between males and females. The immune-regulating kynurenine pathway previously has been implicated in the pathogenesis of mood disorders. In particular, a decreased ratio of neuroprotective (kynurenic acid; KynA) to neurotoxic (3-hydroxykynurenine; 3HK and quinolinic acid; QA) kynurenine pathway metabolites has been reported in several mood disorder subtypes...
September 1, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28866716/blood-serum-concentrations-of-kynurenic-acid-in-patients-diagnosed-with-recurrent-depressive-disorder-depression-in-bipolar-disorder-and-schizoaffective-disorder-treated-with-electroconvulsive-therapy
#5
Marcin Olajossy, Bartosz Olajossy, Sebastian Wnuk, Emilia Potembska, Ewa Urbańska
OBJECTIVES: The aim of the present study was to compare blood serum kynurenic acid (KYNA) concentrations measured before ECT and after 1, 6 and 12 electroconvulsive treatment (ECT) sessions in patients with diagnoses of recurrent depressive disorder (RDD), depression in bipolar disorder (DBD) and schizoaffective disorder (SAD). METHODS: The study group comprised of 50 patients with ICD-10 diagnoses of RDD, DBD and SAD. Blood serum KYNA concentrations were determined and clinical assessment was performed using the MADRS and the GAF scale...
June 18, 2017: Psychiatria Polska
https://www.readbyqxmd.com/read/28840509/kynurenic-acid-prevents-cytoskeletal-disorganization-induced-by-quinolinic-acid-in-mixed-cultures-of-rat-striatum
#6
Paula Pierozan, Helena Biasibetti-Brendler, Felipe Schmitz, Fernanda Ferreira, Regina Pessoa-Pureur, Angela T S Wyse
Kynurenic acid (KYNA) is a neuroactive metabolite of tryptophan known to modulate a number of mechanisms involved in neural dysfunction. Although its activity in the brain has been widely studied, the effect of KYNA counteracting the actions of quinolinic acid (QUIN) remains unknown. The present study aims at describing the ability of 100 μM KYNA preventing cytoskeletal disruption provoked by QUIN in astrocyte/neuron/microglia mixed culture. KYNA totally preserved cytoskeletal organization, cell morphology, and redox imbalance in mixed cultures exposed to QUIN...
August 24, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28825789/multifunctional-analogs-of-kynurenic-acid-for-the-treatment-of-alzheimer-s-disease-synthesis-pharmacology-and-molecular-modeling-studies
#7
Girdhar Singh Deora, Srinivas Kantham, Stephen Chan, Satish N Dighe, Suresh K Veliyath, Gawain McColl, Marie-Odile Parat, Ross P McGeary, Benjamin P Ross
We report the synthesis and pharmacological investigation of analogs of the endogenous molecule kynurenic acid (KYNA) as multifunctional agents for the treatment of Alzheimer's disease (AD). Synthesized KYNA analogs were tested for their N-methyl-d-aspartate (NMDA) receptor binding, mGluR5 binding and function, acetylcholinesterase (AChE) inhibition, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, interference with the amyloid β peptide (Aβ) fibrillation process, and protection against Aβ-induced toxicity in transgenic Caenorhabditis elegans strain GMC101 expressing full-length Aβ42...
September 8, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28814948/synthesis-characterization-cytotoxic-activity-and-interactions-with-ct-dna-and-bsa-of-cationic-ruthenium-ii-complexes-containing-dppm-and-quinoline-carboxylates
#8
Edinaldo N da Silva, Paulo A B da Silva, Angélica E Graminha, Pollyanna F de Oliveira, Jaqueline L Damasceno, Denise C Tavares, Alzir A Batista, Gustavo Von Poelhsitz
The complexes cis-[Ru(quin)(dppm)2]PF6 and cis-[Ru(kynu)(dppm)2]PF6 (quin = quinaldate; kynu = kynurenate; dppm = bis(diphenylphosphino)methane) were prepared and characterized by elemental analysis, electronic, FTIR, (1)H, and (31)P{(1)H} NMR spectroscopies. Characterization data were consistent with a cis arrangement for the dppm ligands and a bidentate coordination through carboxylate oxygens of the quin and kynu anions. These complexes were not able to intercalate CT-DNA as shown by circular dichroism spectroscopy...
2017: Bioinorganic Chemistry and Applications
https://www.readbyqxmd.com/read/28763436/the-beneficial-effects-of-dietary-restriction-on-learning-are-distinct-from-its-effects-on-longevity-and-mediated-by-depletion-of-a-neuroinhibitory-metabolite
#9
Mihir Vohra, George A Lemieux, Lin Lin, Kaveh Ashrafi
In species ranging from humans to Caenorhabditis elegans, dietary restriction (DR) grants numerous benefits, including enhanced learning. The precise mechanisms by which DR engenders benefits on processes related to learning remain poorly understood. As a result, it is unclear whether the learning benefits of DR are due to myriad improvements in mechanisms that collectively confer improved cellular health and extension of organismal lifespan or due to specific neural mechanisms. Using an associative learning paradigm in C...
August 2017: PLoS Biology
https://www.readbyqxmd.com/read/28758944/interactions-between-the-kynurenine-and-the-endocannabinoid-system-with-special-emphasis-on-migraine
#10
REVIEW
Gábor Nagy-Grócz, Ferenc Zádor, Szabolcs Dvorácskó, Zsuzsanna Bohár, Sándor Benyhe, Csaba Tömböly, Árpád Párdutz, László Vécsei
Both the kynurenine and the endocannabinoid systems are involved in several neurological disorders, such as migraine and there are increasing number of reports demonstrating that there are interactions of two systems. Although their cooperation has not yet been implicated in migraine, there are reports suggesting this possibility. Additionally, the individual role of the endocannabinoid and kynurenine system in migraine is reviewed here first, focusing on endocannabinoids, kynurenine metabolites, in particular kynurenic acid...
July 30, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28754152/cerebrospinal-fluid-kynurenine-and-kynurenic-acid-concentrations-are-associated-with-coma-duration-and-long-term-neurocognitive-impairment-in-ugandan-children-with-cerebral-malaria
#11
Dag Holmberg, Elisabeth Franzén-Röhl, Richard Idro, Robert O Opoka, Paul Bangirana, Carl M Sellgren, Ronny Wickström, Anna Färnert, Lilly Schwieler, Göran Engberg, Chandy C John
BACKGROUND: One-fourth of children with cerebral malaria (CM) retain cognitive sequelae up to 2 years after acute disease. The kynurenine pathway of the brain, forming neuroactive metabolites, e.g. the NMDA-receptor antagonist kynurenic acid (KYNA), has been implicated in long-term cognitive dysfunction in other CNS infections. In the present study, the association between the kynurenine pathway and neurologic/cognitive complications in children with CM was investigated. METHODS: Cerebrospinal fluid (CSF) concentrations of KYNA and its precursor kynurenine in 69 Ugandan children admitted for CM to Mulago Hospital, Kampala, Uganda, between 2008 and 2013 were assessed...
July 28, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28748226/peripheral-kynurenine-3-monooxygenase-deficiency-as-a-potential-risk-factor-for-metabolic-syndrome-in-schizophrenia-patients
#12
Gregory Oxenkrug, Marieke van der Hart, Julien Roeser, Paul Summergrad
Increased predisposition of schizophrenia patients (SP) to development of obesity and insulin resistance suggested common signaling pathway between metabolic syndrome (MetS) and schizophrenia. Deficiency of kynurenine-3-monooxygenase (KMO), enzyme catalyzing formation of 3-hydroxykynurenine (3-HK) from kynurenine (Kyn), a tryptophan (Trp) metabolite, might contribute to development of MetS as suggested by non-expression of KMO genes in human fat tissue and elevated serum concentrations of Kyn and its metabolites, kynurenic (KYNA) and anthranilic (ANA) acids, in diabetic patients and Zucker fatty rats (ZFR)...
2017: Integr Clin Med
https://www.readbyqxmd.com/read/28735520/gemst-a-taylor-made-combination-that-reverts-neuroanatomical-changes-in-stroke
#13
Arturo Mangas, Javier Yajeya, Noelia González, Isabel Ruiz, Marianny Pernìa, Michel Geffard, Rafael Coveñas
In a single transient middle cerebral artery occlusion model of stroke and using immunohistochemical techniques, the effects of a new therapeutic approach named Gemst (a member of the Poly-L-Lysine innovative therapies) have been studied in the rat brain. The expression of inflammatory (CD45, CD11b), oxidative (NO-tryptophan, NO2-tyrosine) and indoleamine 2, 3-dioxygenase pathway (kynurenic acid, 3-hydroxy anthranilic acid) markers has been evaluated in early and late phases of stroke. For this purpose, we have developed eight highly specific monoclonal antibodies directed against some of these markers...
May 25, 2017: European Journal of Histochemistry: EJH
https://www.readbyqxmd.com/read/28733707/angiotensin-ii-type-1-receptor-blockers-inhibit-kat-ii-activity-in-the-brain-its-possible-clinical-applications
#14
Izabela Zakrocka, Katarzyna M Targowska-Duda, Artur Wnorowski, Tomasz Kocki, Krzysztof Jóźwiak, Waldemar A Turski
Angiotensin II receptor blockers (ARBs) are one of the most frequently recommended antihypertensive drugs. Apart from their activity towards the circulatory system, ARBs also penetrate the blood-brain barrier and display neuroprotective effects. Kynurenic acid (KYNA) is an endogenous metabolite of tryptophan produced by kynurenine aminotransferase II (KAT II) in the brain. Antagonism towards all ionotropic glutamate (GLU) receptors is the main mechanism of KYNA action. An elevated brain level of KYNA is linked with memory impairment and psychotic symptoms...
July 21, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28731451/novel-blood-based-biomarkers-of-cognition-stress-and-physical-or-cognitive-training-in-older-adults-at-risk-of-dementia-preliminary-evidence-for-a-role-of-bdnf-irisin-and-the-kynurenine-pathway
#15
Olivia C Küster, Daria Laptinskaya, Patrick Fissler, Cathrin Schnack, Martina Zügel, Verena Nold, Franka Thurm, Sina Pleiner, Alexander Karabatsiakis, Björn von Einem, Patrick Weydt, André Liesener, Andreas Borta, Alexander Woll, Bastian Hengerer, Iris-Tatjana Kolassa, Christine A F von Arnim
 Psychosocial stress and physical, cognitive, and social activity predict the risk of cognitive decline and dementia. The aim of this study was to elucidate brain-derived neurotrophic factor (BDNF), irisin, and the kynurenine pathway (KP) as potential underlying biological correlates. We evaluated associations of irisin and the KP with BDNF in serum and with cognition, stress, and activities. Furthermore, changes in serum concentrations of BDNF, irisin, and KP metabolites were investigated after physical or cognitive training...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28729445/preferential-disruption-of-prefrontal-gabaergic-function-by-nanomolar-concentrations-of-the-%C3%AE-7nach-negative-modulator-kynurenic-acid
#16
Eden Flores-Barrera, Daniel R Thomases, Daryn K Cass, Ajay Bhandari, Robert Schwarcz, John P Bruno, Kuei Y Tseng
Increased concentrations of kynurenic acid (KYNA) in the prefrontal cortex (PFC) are thought to contribute to the development of cognitive deficits observed in schizophrenia. Although this view is consistent with preclinical studies showing a negative impact of prefrontal KYNA elevation on executive function, the mechanism underlying such a disruption remains unclear. Here, we measured changes in local field potential (LFP) responses to ventral hippocampal stimulation in vivo and conducted whole-cell patch-clamp recordings in brain slices to reveal how nanomolar concentrations of KYNA alter synaptic transmission in the PFC of male adult rats...
August 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28726741/magnolol-a-natural-polyphenol-attenuates-dextran-sulfate-sodium-induced-colitis-in-mice
#17
Ling Zhao, Hai-Tao Xiao, Huai-Xue Mu, Tao Huang, Ze-Si Lin, Linda L D Zhong, Guang-Zhi Zeng, Bao-Min Fan, Cheng-Yuan Lin, Zhao-Xiang Bian
Magnolol is a lignan with anti-inflammatory activity identified in Magnolia officinalis. Ulcerative colitis (UC), one of the types of inflammatory bowel disease (IBD), is a disease that causes inflammation and ulcers in the colon. To investigate the effect of magnolol in dextran sulfate sodium (DSS)-induced experimental UC model, male C57 mice were treated with 2% DSS drinking water for 5 consecutive days followed by intragastric administration with magnolol (5, 10 and 15 mg/kg) daily for 7 days. The results showed that magnolol significantly attenuated disease activity index, inhibited colonic shortening, reduced colonic lesions and suppressed myeloperoxidase (MPO) activity...
July 20, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28712413/sleep-disturbance-and-kynurenine-metabolism-in-depression
#18
Hyong Jin Cho, Jonathan Savitz, Robert Dantzer, T Kent Teague, Wayne C Drevets, Michael R Irwin
OBJECTIVE: Although the interrelationships between sleep disturbance, inflammation, and depression have been found, molecular mechanisms that link these conditions are largely unknown. Kynurenine metabolism is hypothesized to be a key mechanism that links inflammation and depression. Inflammation activates the kynurenine pathway, leading to increases in 3-hydroxykynurenine (3HK) and quinolinic acid (QA), potentially neurotoxic metabolites, and decreases in kynurenic acid (KynA), a potentially neuroprotective compound...
August 2017: Journal of Psychosomatic Research
https://www.readbyqxmd.com/read/28710517/urinary-profiling-of-tryptophan-and-its-related-metabolites-in-patients-with-metabolic-syndrome-by-liquid-chromatography-electrospray-ionization-mass-spectrometry
#19
Ji Sun Oh, Hong Seong Seo, Kyoung Heon Kim, Heesoo Pyo, Bong Chul Chung, Jeongae Lee
Tryptophan (Trp) is an essential amino acid that plays an important role in protein synthesis and is a precursor of various substances related to diverse biological functions. An imbalance in Trp metabolites is associated with inflammatory diseases. The accurate and precise measurement of these compounds in biological specimens would provide meaningful information for understanding the biochemical states of various metabolic syndrome-related diseases, such as hyperlipidemia, hypertension, diabetes, and obesity...
July 14, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28709913/upregulation-of-neuronal-kynurenine-3-monooxygenase-mediates-depression-like-behavior-in-a-mouse-model-of-neuropathic-pain
#20
Geoffroy Laumet, Wenjun Zhou, Robert Dantzer, Jules D Edralin, XiaoJiao Huo, David P Budac, Jason C O'Connor, Anna W Lee, Cobi J Heijnen, Annemieke Kavelaars
Pain and depression often co-occur, but the underlying mechanisms have not been elucidated. Here, we used the spared nerve injury (SNI) model in mice to induce both neuropathic pain and depression-like behavior. We investigated whether brain interleukin (IL)-1 signaling and activity of kynurenine 3-monoxygenase (KMO), a key enzyme for metabolism of kynurenine into the neurotoxic NMDA receptor agonist quinolinic acid, are necessary for comorbid neuropathic pain and depression-like behavior. SNI mice showed increased expression levels of Il1b and Kmo mRNA in the contralateral side of the brain...
July 11, 2017: Brain, Behavior, and Immunity
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