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https://www.readbyqxmd.com/read/28901278/neuroinflammation-and-the-immune-kynurenine-pathway-in-anxiety-disorders
#1
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
#2
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
#3
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
#4
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
#5
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...
August 30, 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
#6
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/28831293/3-hydroxykynurenine-and-3-hydroxyanthranilic-acid-enhance-the-toxicity-induced-by-copper-in-rat-astrocyte-culture
#7
Daniela Ramírez-Ortega, Alelí Ramiro-Salazar, Dinora González-Esquivel, Camilo Ríos, Benjamín Pineda, Verónica Pérez de la Cruz
Copper is an integral component of various enzymes, necessary for mitochondrial respiration and other biological functions. Excess copper is related with neurodegenerative diseases as Alzheimer and is able to modify cellular redox environment, influencing its functions, signaling, and catabolic pathways. Tryptophan degradation through kynurenine pathway produces some metabolites with redox properties as 3-hydroxykynurenine (3-HK) and 3-hydroxyanthranilic acid (3-HANA). The imbalance in their production is related with some neuropathologies, where the common factors are oxidative stress, inflammation, and cell death...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28827067/increased-tryptophan-metabolism-is-associated-with-activity-of-inflammatory-bowel-diseases
#8
Susanna Nikolaus, Berenice Schulte, Natalie Al-Massad, Florian Thieme, Dominik M Schulte, Johannes Bethge, Ateequr Rehman, Florian Tran, Konrad Aden, Robert Häsler, Natalie Moll, Gregor Schütze, Markus J Schwarz, Georg H Waetzig, Philip Rosenstiel, Michael Krawczak, Silke Szymczak, Stefan Schreiber
BACKGROUND & AIMS: Administration of tryptophan, and some of its metabolites, reduces the severity of colitis in mice, whereas removing tryptophan from the diet increases susceptibility to colitis. Transfer of the intestinal microbiome can increase susceptibility of mice to colitis. We aimed to systematically evaluate serum levels of tryptophan and its metabolites in patients with inflammatory bowel diseases (IBD), and study their association with clinical and serologic features. METHODS: We studied 535 consecutive patients with IBD (211 with ulcerative colitis [UC], 234 with Crohn's disease [CD]; 236 male), enrolled in Germany from August 2013 through April 2014 and followed until July 2016...
August 18, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28825789/multifunctional-analogs-of-kynurenic-acid-for-the-treatment-of-alzheimer-s-disease-synthesis-pharmacology-and-molecular-modeling-studies
#9
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/28821813/metabolomic-and-lipidomic-profiling-identifies-the-role-of-the-rna-editing-pathway-in-endometrial-carcinogenesis
#10
Tatiana Altadill, Tyrone M Dowdy, Kirandeep Gill, Armando Reques, Smrithi S Menon, Cristian P Moiola, Carlos Lopez-Gil, Eva Coll, Xavier Matias-Guiu, Silvia Cabrera, Angel Garcia, Jaume Reventos, Stephen W Byers, Antonio Gil-Moreno, Amrita K Cheema, Eva Colas
Endometrial cancer (EC) remains the most common malignancy of the genital tract among women in developed countries. Although much research has been performed at genomic, transcriptomic and proteomic level, there is still a significant gap in the metabolomic studies of EC. In order to gain insights into altered metabolic pathways in the onset and progression of EC carcinogenesis, we used high resolution mass spectrometry to characterize the metabolomic and lipidomic profile of 39 human EC and 17 healthy endometrial tissue samples...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28792876/nad-deficiency-congenital-malformations-and-niacin-supplementation
#11
Hongjun Shi, Annabelle Enriquez, Melissa Rapadas, Ella M M A Martin, Roni Wang, Julie Moreau, Chai K Lim, Justin O Szot, Eddie Ip, James N Hughes, Kotaro Sugimoto, David T Humphreys, Aideen M McInerney-Leo, Paul J Leo, Ghassan J Maghzal, Jake Halliday, Janine Smith, Alison Colley, Paul R Mark, Felicity Collins, David O Sillence, David S Winlaw, Joshua W K Ho, Gilles J Guillemin, Matthew A Brown, Kazu Kikuchi, Paul Q Thomas, Roland Stocker, Eleni Giannoulatou, Gavin Chapman, Emma L Duncan, Duncan B Sparrow, Sally L Dunwoodie
BACKGROUND: Congenital malformations can be manifested as combinations of phenotypes that co-occur more often than expected by chance. In many such cases, it has proved difficult to identify a genetic cause. We sought the genetic cause of cardiac, vertebral, and renal defects, among others, in unrelated patients. METHODS: We used genomic sequencing to identify potentially pathogenic gene variants in families in which a person had multiple congenital malformations...
August 10, 2017: New England Journal of Medicine
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
#12
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/28751584/kynurenines-tryptophan-s-metabolites-in-exercise-inflammation-and-mental-health
#13
REVIEW
Igor Cervenka, Leandro Z Agudelo, Jorge L Ruas
Kynurenine metabolites are generated by tryptophan catabolism and regulate biological processes that include host-microbiome signaling, immune cell response, and neuronal excitability. Enzymes of the kynurenine pathway are expressed in different tissues and cell types throughout the body and are regulated by cues, including nutritional and inflammatory signals. As a consequence of this systemic metabolic integration, peripheral inflammation can contribute to accumulation of kynurenine in the brain, which has been associated with depression and schizophrenia...
July 28, 2017: Science
https://www.readbyqxmd.com/read/28740612/3-hydroxykynurenine-a-tryptophan-metabolite-generated-during-the-infection-is-active-against-trypanosoma-cruzi
#14
Carolina P Knubel, Constanza Insfran, Fernando F Martinez, Cintia Diaz Lujan, Ricardo E Fretes, Martin G Theumer, Laura Cervi, Claudia C Motran
The antiparasitic activity of 3-hydroxykynurenine (3-HK), one of the major tryptophan catabolites of the kynurenine pathway, against both Trypanosoma cruzi evolutive forms that are important for human infection, trypomastigotes (Tps) and amastigotes (Am), possible targets in the parasite and the drug toxicity to mammalian cells have been investigated. 3-HK showed a potent activity against Am with IC50 values in the micromolar concentration range, while the IC50 values to cause Tps death was ∼6000-times higher, indicating that the replicative form present in the vertebrate hosts is much more susceptible to 3-HK than bloodstream Tps...
July 13, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28740260/richer-gut-microbiota-with-distinct-metabolic-profile-in-hiv-infected-elite-controllers
#15
Jan Vesterbacka, Javier Rivera, Kajsa Noyan, Mariona Parera, Ujjwal Neogi, Malu Calle, Roger Paredes, Anders Sönnerborg, Marc Noguera-Julian, Piotr Nowak
Gut microbiota dysbiosis features progressive HIV infection and is a potential target for intervention. Herein, we explored the microbiome of 16 elite controllers (EC), 32 antiretroviral therapy naive progressors and 16 HIV negative controls. We found that the number of observed genera and richness indices in fecal microbiota were significantly higher in EC versus naive. Genera Succinivibrio, Sutterella, Rhizobium, Delftia, Anaerofilum and Oscillospira were more abundant in EC, whereas Blautia and Anaerostipes were depleted...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28738353/inflammation-effects-on-glutamate-as-a-pathway-to-neuroprogression-in-mood-disorders
#16
Ebrahim Haroon, Andrew H Miller
Neuroprogression is a term used to describe worsening psychopathology, poor treatment response, and declining cognitive and functional outcomes among patients with chronic mental disorders. Chronic inflammatory activation and glutamate-mediated excitotoxicity are two key etiological factors implicated in the development of neuroprogression. In this chapter, we hypothesize that the association between chronic inflammatory activation, neuroprogression, and glutamate dysregulation might be mediated by glial dysfunction...
2017: Modern Trends in Pharmacopsychiatry
https://www.readbyqxmd.com/read/28738351/major-depression-as-a-neuroprogressive-prelude-to-dementia-what-is-the-evidence
#17
Brian E Leonard
Epidemiological studies implicate chronic depression as a predisposing factor for dementia in later life. However, the link is incompletely understood and controversial. The aim of this review is to consider some of the biological factors that contribute to neuroprogressive brain dysfunction in late life as a consequence of prolonged, low-grade inflammation in the course of depressive episodes. As chronic inflammation is known to precipitate increased apoptosis of neurons and astrocytes, this could be a contributing factor to brain dysfunction...
2017: Modern Trends in Pharmacopsychiatry
https://www.readbyqxmd.com/read/28736331/microbial-regulation-of-hippocampal-mirna-expression-implications-for-transcription-of-kynurenine-pathway-enzymes
#18
Gerard M Moloney, Olivia F O'Leary, Eloisa Salvo-Romero, Lieve Desbonnet, Fergus Shanahan, Timothy G Dinan, Gerard Clarke, John F Cryan
Increasing evidence points to a functional role of the enteric microbiota in brain development, function and behaviour including the regulation of transcriptional activity in the hippocampus. Changes in CNS miRNA expression may reflect the colonisation status of the gut. Given the pivotal impact of miRNAs on gene expression, our study was based on the hypothesis that gene expression would also be altered in the germ-free state in the hippocampus. We measured miRNAs in the hippocampus of Germ free (GF), conventional (C) and Germ free colonised (exGF) Swiss Webster mice...
July 20, 2017: Behavioural Brain 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
#19
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/28723608/breastfeeding-and-the-gut-brain-axis-is-there-a-role-for-melatonin
#20
REVIEW
George Anderson, Cathy Vaillancourt, Michael Maes, Russel J Reiter
The benefits of breastfeeding over formula feed are widely appreciated. However, for many mothers breastfeeding is not possible, highlighting the need for a significant improvement in the contents of formula feed. In this article, the overlooked role of melatonin and the melatonergic pathways in breast milk and in the regulation of wider breast milk components are reviewed. There is a growing appreciation that the benefits of breastfeeding are mediated by its effects in the infant gut, with consequences for the development of the gut-brain axis and the immune system...
September 26, 2017: Biomolecular Concepts
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