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"kynurenine pathway"

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https://www.readbyqxmd.com/read/29126954/quantitative-analysis-of-kynurenine-aminotransferase-ii-in-the-adult-rat-brain-reveals-high-expression-in-proliferative-zones-and-corpus-callosum
#1
Chang Song, Sarah M Clark, Chloe N Vaughn, James D Nicholson, Kelley J Murphy, Ta-Chung M Mou, Robert Schwarcz, Gloria E Hoffman, Leonardo H Tonelli
Kynurenic acid, a metabolite of the kynurenine pathway of tryptophan degradation, acts as an endogenous antagonist of alpha7 nicotinic and NMDA receptors and is implicated in a number of neurophysiological and neuropathological processes including cognition and neurodegenerative events. Therefore, kynurenine aminotransferase II (KAT II/AADAT), the enzyme responsible for the formation of the majority of neuroactive kynurenic acid in the brain, has prompted significant interest. Using immunohistochemistry, this enzyme was localized primarily in astrocytes throughout the adult rat brain, but detailed neuroanatomical studies are lacking...
November 7, 2017: Neuroscience
https://www.readbyqxmd.com/read/29103054/is-the-enzyme-acmsd-a-novel-therapeutic-target-in-parkinson-s-disease
#2
Keerthi Thirtamara-Rajamani, Peipei Li, Martha L Escobar Galvis, Viviane Labrie, Patrik Brundin, Lena Brundin
 Several large genome wide association studies have identified a locus in close proximity to the gene encoding the enzyme aminocarboxymuconate-semialdehyde-decarboxylase (ACMSD) to be associated with the risk for Parkinson's disease (PD), tentatively suggesting that this enzyme might influence PD pathogenesis. Further support for this comes from the recent identification of a disease-segregating stop codon mutation in ACMSD in a family with Parkinsonism, and a missense mutation in the ACMSD gene predicted to disrupt enzyme function in an individual with typical PD...
2017: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/29080891/prenatal-dynamics-of-kynurenine-pathway-metabolism-in-mice-focus-on-kynurenic-acid
#3
Nick Goeden, Francesca M Notarangelo, Ana Pocivavsek, Sarah Beggiato, Alexandre Bonnin, Robert Schwarcz
The kynurenine pathway (KP), the major catabolic route of tryptophan in mammals, contains several neuroactive metabolites, including kynurenic acid (KYNA) and 3-hydroxykynurenine (3-HK). KP metabolism, and especially the fate of KYNA, during pregnancy is poorly understood, yet it may play a significant role in the development of psychiatric disorders later in life. The present study was designed to investigate the prenatal features of KP metabolism in vivo, with special focus on KYNA. To this end, pregnant CD-1 mice were treated systemically with kynurenine (100 mg/kg), KYNA (10 mg/kg), or saline on embryonic day 18...
October 28, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/29069807/chronic-high-dose-of-captopril-induces-depressive-like-behaviors-in-mice-possible-mechanism-of-regulatory-t-cell-in-depression
#4
Hyun-Sun Park, Arum Han, Hye-Lim Yeo, Min-Jung Park, Min-Jung You, Hyun Jin Choi, Chang-Won Hong, Sang-Hyuk Lee, Seung Hyun Kim, Borah Kim, Min-Soo Kwon
Major depression has various types of symptoms and disease courses with inconsistent response to monoamine-related antidepressants. Thus, monoamine theory may not be the only pathophysiologic pathway relevant to depression. Recently, it has been suggested that regulatory T cell (Treg) is associated with depression. Based on our previous study that showed decreased regulatory T cell (Treg) population following chronic high-dose captopril (CHC, 40 mg/kg/day * 21 days) administration, we examined whether CHC alone can induce depressive-like behaviors in mice even without stressful stimuli...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29065338/differences-in-the-association-of-inflammation-and-tryptophan-with-depressive-symptoms-between-white-and-non-white-chronic-dialysis-patients
#5
Gertrud L Haverkamp, Wim L Loosman, Robbert W Schouten, Casper F Franssen, Ido P Kema, Merel van Diepen, Friedo W Dekker, Carl E Siegert, Adriaan Honig
OBJECTIVE: Possibly, different biochemical parameters are involved in the development of depressive symptoms in white and non-white dialysis patients. We examined whether the association between inflammation and depressive symptoms and between tryptophan and depressive symptoms differs between white and non-white dialysis patients and whether the association between inflammation and depressive symptoms is mediated by tryptophan degradation along the kynurenine pathway in both groups. METHOD: Depressive symptoms were measured with the BDI-II...
October 13, 2017: General Hospital Psychiatry
https://www.readbyqxmd.com/read/29051706/investigation-of-the-tissue-distribution-and-physiological-roles-of-indoleamine-2-3-dioxygenase-2
#6
Felicita F Jusof, Supun M Bakmiwewa, Silvia Weiser, Lay Khoon Too, Richard Metz, George C Prendergast, Stuart T Fraser, Nicholas H Hunt, Helen J Ball
Indoleamine 2,3-dioxygenase-2 (IDO2) is 1 of the 3 enzymes that can catalyze the first step in the kynurenine pathway of tryptophan metabolism. Of the 2 other enzymes, tryptophan 2,3-dioxygenase is highly expressed in the liver and has a role in tryptophan homeostasis, whereas indoleamine 2,3-dioxygenase-1 (IDO1) expression is induced by inflammatory stimuli. Indoleamine 2,3-dioxygenase-2 is reportedly expressed comparatively narrow, including in liver, kidney, brain, and in certain immune cell types, and it does not appear to contribute significantly to systemic tryptophan catabolism under normal physiological conditions...
2017: International Journal of Tryptophan Research: IJTR
https://www.readbyqxmd.com/read/29038460/a-novel-immunohistochemical-score-to-predict-early-mortality-in-acute-myeloid-leukemia-patients-based-on-indoleamine-2-3-dioxygenase-expression
#7
Abhishek Mangaonkar, Ashis Kumar Mondal, Sadanand Fulzule, Chetan Pundkar, Eun Jeong Park, Anand Jillella, Vamsi Kota, Hongyan Xu, Natasha M Savage, Huidong Shi, David Munn, Ravindra Kolhe
Indoleamine 2,3 dioxygenase-1 (IDO-1) is an enzyme in the kynurenine pathway which augments tumor-induced immune tolerance. Previous studies in childhood acute myeloid leukemia (AML) have shown a negative correlation of IDO-1 mRNA expression with outcomes. The aim of our study was to develop a practical and objective immunohistochemical technique to quantify IDO-1 expression on diagnostic bone marrow biopsies of AML patients in order to facilitate its use in routine clinical practice. IDO-1 mRNA was extracted from diagnostic bone marrow specimens from 29 AML patients...
October 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29033891/commentary-the-effect-of-systemic-nitroglycerin-administration-on-the-kynurenine-pathway-in-the-rat
#8
COMMENT
Marcelo Moraes Valença
No abstract text is available yet for this article.
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/29031603/xanthurenic-acid-formation-from-3-hydroxykynurenine-in-the-mammalian-brain-neurochemical-characterization-and-physiological-effects
#9
K V Sathyasaikumar, M Tararina, H-Q Wu, S A Neale, F Weisz, T E Salt, R Schwarcz
Xanthurenic acid (XA), formed from 3-hydroxykynurenine (3-HK) in the kynurenine pathway of tryptophan degradation, may modulate glutamatergic neurotransmission by inhibiting the vesicular glutamate transporter and/or activating Group II metabotropic glutamate receptors. Here we examined the molecular and cellular mechanisms by which 3-HK controls the neosynthesis of XA in rat, mouse and human brain, and compared the physiological actions of 3-HK and XA in the rat brain. In tissue homogenates, XA formation from 3-HK was observed in all three species and traced to a major role of kynurenine aminotransferase II (KAT II)...
October 12, 2017: Neuroscience
https://www.readbyqxmd.com/read/29030243/the-inhibition-of-the-kynurenine-pathway-prevents-behavioral-disturbances-and-oxidative-stress-in-the-brain-of-adult-rats-subjected-to-an-animal-model-of-schizophrenia
#10
Gislaine Z Réus, Indianara R T Becker, Giselli Scaini, Fabricia Petronilho, Jean P Oses, Rima Kaddurah-Daouk, Luciane B Ceretta, Alexandra I Zugno, Felipe Dal-Pizzol, João Quevedo, Tatiana Barichello
Evidence has shown that the kynurenine pathway (KP) plays a role in the onset of oxidative stress and also in the pathophysiology of schizophrenia. The aim of this study was to use a pharmacological animal model of schizophrenia induced by ketamine to investigate if KP inhibitors could protect the brains of Wistar rats against oxidative stress and behavioral changes. Ketamine, injected at the dose of 25mg/kg, increased spontaneous locomotor activity. However, the inhibitors of tryptophan 2,3-dioxygenase (TDO), indoleamine 2,3-dioxygenase (IDO) and kynurenine-3-monooxygenase (KMO) were able to reverse these changes...
October 13, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29029302/acute-kynurenine-challenge-disrupts-sleep-wake-architecture-and-impairs-contextual-memory-in-adult-rats
#11
Ana Pocivavsek, Annalisa M Baratta, Jessica A Mong, Shaun S Viechweg
Study Objectives: Tryptophan metabolism via the kynurenine pathway may represent a key molecular link between sleep loss and cognitive dysfunction. Modest increases in the kynurenine pathway metabolite kynurenic acid (KYNA), which acts as an antagonist at N-methyl-d-aspartate and α7 nicotinic acetylcholine receptors in the brain, result in cognitive impairments. As glutamatergic and cholinergic neurotransmissions are critically involved in modulation of sleep, our current experiments tested the hypothesis that elevated KYNA adversely impacts sleep quality...
September 28, 2017: Sleep
https://www.readbyqxmd.com/read/29016635/hiv-human-herpesvirus-co-infections-impact-on-tryptophan-kynurenine-pathway-and-immune-reconstitution
#12
Siew Hwei Yap, Noor Kamila Abdullah, Megan McStea, Kozo Takayama, Meng Li Chong, Elisa Crisci, Marie Larsson, Iskandar Azwa, Adeeba Kamarulzaman, Kok Hoong Leong, Yin Ling Woo, Reena Rajasuriar
BACKGROUND: Co-infections with human herpesvirus (HHV) have been associated with residual chronic inflammation in antiretroviral (ART)-treated human immunodeficiency virus (HIV)-infected individuals. However, the role of HHV in modulating the tryptophan-kynurenine pathway and clinical outcomes in HIV-infected individuals is poorly understood. Thus, we investigated the seroprevalence of four common HHVs among treated HIV-infected participants and their impact on kynurenine/tryptophan (K/T) ratio and long-term CD4 T-cell recovery in HIV/HHV co-infected participants...
2017: PloS One
https://www.readbyqxmd.com/read/28978552/tryptophan-derived-3-hydroxyanthranilic-acid-contributes-to-angiotensin-ii-induced-abdominal-aortic-aneurysm-formation-in-mice-in-vivo
#13
Qiongxin Wang, Ye Ding, Ping Song, Huaiping Zhu, Imoh S Okon, Nan-Yang Ding, Houzao Chen, Depei Liu, Ming-Hui Zou
Background -Abnormal amino acid metabolism is associated with vascular disease. However, the causative link between dysregulated tryptophan metabolism and abdominal aortic aneurysm (AAA) is unknown. Methods -Indoleamine 2,3-dioxygenase (IDO) is the first and rate-limiting enzyme in the kynurenine pathway of tryptophan metabolism. Mice with deficiencies in both apolipoprotein e (Apoe) and IDO (Apoe(-/-)/IDO(-/-)) were generated by cross-breeding IDO(-/-) mice with Apoe(-/-) mice. Results -The acute infusion of angiotensin II (AngII) markedly increased the incidence of AAA in Apoe(-/-) mice, but not in Apoe(-/-)/IDO(-/-) mice, which presented decreased elastic lamina degradation and aortic expansion...
October 4, 2017: Circulation
https://www.readbyqxmd.com/read/28955772/modulation-of-host-hif-1%C3%AE-activity-and-the-tryptophan-pathway-contributes-to-the-anti-toxoplasma-gondii-potential-of-nanoparticles
#14
Oluyomi Stephen Adeyemi, Yuho Murata, Tatsuki Sugi, Yongmei Han, Kentaro Kato
BACKGROUND: Toxoplasmosis constitutes a large global burden that is further exacerbated by the shortcomings of available therapeutic options, thus underscoring the urgent need for better anti-Toxoplasma gondii therapy or strategies. Recently, we showed that the anti-parasitic action of inorganic nanoparticles (NPs) could, in part, be due to changes in redox status as well as in the parasite mitochondrial membrane potential. METHODS: In the present study, we explored the in vitro mode of action of the anti-T...
September 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/28901278/neuroinflammation-and-the-immune-kynurenine-pathway-in-anxiety-disorders
#15
Yong-Ku Kim, Sang Won Jeon
BACKGROUND: Recently, neuroinflammation and the immune-kynurenine pathway have received increased attention in the psychoimmunology field of major depressive disorder (MDD), while studies related to anxiety disorders have been very limited. OBJECTIVE: This study reviewed possible mechanisms by which stress or inflammation modulate anxiety through tryptophan metabolism and the kynurenine pathway. METHOD: Relevant literature was identified through a search of MEDLINE via PubMed...
September 12, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28899580/the-interplay-between-cytokines-and-the-kynurenine-pathway-in-inflammation-and-atherosclerosis
#16
Roland Baumgartner, Maria J Forteza, Daniel F J Ketelhuth
The kynurenine pathway (KP) is the major metabolic route of tryptophan (Trp) metabolism. Indoleamine 2,3-dioxygenase (IDO1), the enzyme responsible for the first and rate-limiting step in the pathway, as well as other enzymes in the pathway, have been shown to be highly regulated by cytokines. Hence, the KP has been implicated in several pathologic conditions, including infectious diseases, psychiatric disorders, malignancies, and autoimmune and chronic inflammatory diseases. Additionally, recent studies have linked the KP with atherosclerosis, suggesting that Trp metabolism could play an essential role in the maintenance of immune homeostasis in the vascular wall...
September 9, 2017: Cytokine
https://www.readbyqxmd.com/read/28879460/vitamin-b6-reduces-neurochemical-and-long-term-cognitive-alterations-after-polymicrobial-sepsis-involvement-of-the-kynurenine-pathway-modulation
#17
Lucinéia Gainski Danielski, Amanda Della Giustina, Mariana Pereira Goldim, Drielly Florentino, Khiany Mathias, Leandro Garbossa, Rosiane de Bona Schraiber, Ana Olívia Martins Laurentino, Marina Goulart, Monique Michels, Karina Barbosa de Queiroz, Markus Kohlhof, Gislaine Tezza Rezin, Jucélia Jeremias Fortunato, Joao Quevedo, Tatiana Barichello, Felipe Dal-Pizzol, Roney S Coimbra, Fabricia Petronilho
Neurological dysfunction as a result of neuroinflammation has been reported in sepsis and cause high mortality. High levels of cytokines stimulate the formation of neurotoxic metabolites by kynurenine (KYN) pathway. Vitamin B6 (vit B6) has anti-inflammatory and antioxidant properties and also acts as a cofactor for enzymes of the KYN pathway. Thus, by using a relevant animal model of polymicrobial sepsis, we studied the effect of vit B6 on the KYN pathway, acute neurochemical and neuroinflammatory parameters, and cognitive dysfunction in rats...
September 6, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28871782/antibiotic-treatment-preventing-necrotising-enterocolitis-alters-urinary-and-plasma-metabolomes-in-preterm-pigs
#18
Pingping Jiang, Alessia Trimigno, Jan Stanstrup, Bekzod Khakimov, Nanna Viereck, Søren Balling Engelsen, Per Torp Sangild, Lars Ove Dragsted
Necrotising enterocolitis (NEC) is a serious gut inflammatory condition in premature neonates, onset and development of which depend on the gut microbiome. Attenuation of the gut microbiome by antibiotics can reduce NEC incidence and severity. However, how the antibiotics-suppressed gut microbiome affects the whole-body metabolism in NEC-sensitive premature neonates is unknown. In formula-fed preterm pigs, used as a model for preterm infants, plasma and urinary metabolomes were investigated by LC-MS and (1)H NMR, with and without antibiotic treatment immediately after birth...
September 14, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28869479/kynurenine-pathway-metabolites-in-alzheimer-s-disease
#19
Lasse Melvaer Giil, Øivind Midttun, Helga Refsum, Arve Ulvik, Rajiv Advani, A David Smith, Per Magne Ueland
BACKGROUND: Metabolites of tryptophan, produced via the kynurenine pathway (kynurenines), have been linked to Alzheimer's disease (AD) in small cohorts with conflicting results. OBJECTIVE: To compare differences in plasma kynurenine levels between AD and controls and identify potential associations with cognition. METHODS: The study included 65 histopathologically-confirmed AD patients and 65 cognitively-screened controls from the Oxford Project to Investigate Memory and Ageing (OPTIMA) cohort...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28867283/kynurenic-acid-is-reduced-in-females-and-oral-contraceptive-users-implications-for-depression
#20
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
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