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https://www.readbyqxmd.com/read/28442354/the-influence-of-stress-on-neuroinflammation-and-alterations-in-brain-structure-and-function-in-major-depressive-disorder
#1
REVIEW
Yong-Ku Kim, Eunsoo Won
Major depressive disorder (MDD) is a condition which has often been associated with chronic stress. The sympathetic nervous system is continuously activated without the normal counteraction of the parasympathetic nervous system under the influence of chronic stress. As a result, epinephrine and norepinephrine levels are increased, and acetylcholine levels are decreased, which in turn can increase the levels of pro-inflammatory cytokines. Peripheral inflammatory responses can access the brain, with neuroinflammation contributing to the increase in neurotoxic kynurenine pathway metabolites such as 3-hydroxykynurenine, 3-hydroxyanthranilic acid and quinolinic acid, and decrease in neuroprotective metabolites such as kynurenic acid...
April 22, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28431630/kynurenic-acid-and-its-analogue-can-alter-the-opioid-receptor-g-protein-signaling-after-acute-treatment-via-nmda-receptor-in-rat-cortex-and-striatum
#2
Reza Samavati, Ferenc Zádor, Edina Szűcs, Bernadett Tuka, Diána Martos, Gábor Veres, Róbert Gáspár, István M Mándity, Ferenc Fülöp, László Vécsei, Sándor Benyhe, Anna Borsodi
Previously, we have shown that the N-methyl d-aspartate (NMDA)-receptor antagonist kynurenic acid (KYNA) and its analogue KYNA1 do not bind directly to mu, kappa and delta opioid receptors in vitro. On the other hand, chronic administration of KYNA and KYNA1 resulted in region (cortex vs striatum) and opioid receptor-type specific alterations in G-protein activation of mouse brain homogenates. Here we describe for the first time the acute effect of KYNA and KYNA1 on opioid receptor function with the possible involvement of the NMDA receptor...
May 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28426698/extensive-alterations-of-blood-metabolites-in-pediatric-cerebral-malaria
#3
Sanchit Gupta, Karl Seydel, Miguel A Miranda-Roman, Catherine M Feintuch, Alex Saidi, Ryung S Kim, Gretchen L Birbeck, Terrie Taylor, Johanna P Daily
Cerebral malaria (CM) presents as an encephalopathy and is due to infection with Plasmodium falciparum. Patients are comatose, often with fever, recurrent seizures and this condition is associated with a high mortality rate. The etiology of the coma and seizures are poorly understood. Circulating small molecules and lipids have bioactive functions and alterations in their concentrations have been implicated in seizure disorders and other forms of encephalopathy. We carried out a comprehensive analysis of blood metabolites during CM to explore a biochemical basis of this encephalopathy...
2017: PloS One
https://www.readbyqxmd.com/read/28419874/oral-administration-of-a-specific-kynurenic-acid-synthesis-kat-ii-inhibitor-attenuates-evoked-glutamate-release-in-rat-prefrontal-cortex
#4
D M Bortz, H-Q Wu, R Schwarcz, J P Bruno
Cognitive deficits represent core symptoms in schizophrenia (SZ) and predict patient outcome; however, they remain poorly treated by current antipsychotic drugs. Elevated levels of the endogenous alpha7 nicotinic receptor negative allosteric modulator and NMDA receptor antagonist, kynurenic acid (KYNA), are commonly seen in post-mortem tissue and cerebrospinal fluid of patients with SZ. When acutely or chronically elevated in rodents, KYNA produces cognitive deficits similar to those seen in the disease, making down-regulation of KYNA, via inhibition of kynurenine aminotransferase II (KAT II), a potential treatment strategy...
April 15, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28408830/twelve-week-physical-exercise-does-not-have-a-long-lasting-effect-on-kynurenines-in-plasma-of-depressed-patients
#5
Vincent Millischer, Sophie Erhardt, Örjan Ekblom, Yvonne Forsell, Catharina Lavebratt
BACKGROUND: Physical exercise has well-characterized positive effects on depressive symptoms. The underlying biologic mechanisms are, however, far from established. A recently discovered mechanism has linked the enhanced conversion of kynurenine to kynurenic acid (KYNA) to an increased resilience toward stress-induced depression in mice. The aim of this study was to translate these findings to humans. MATERIALS AND METHODS: Kynurenine and KYNA levels were measured by high-performance liquid chromatography in plasma samples from 117 patients affected by mild-to-moderate depression before and within a week after a 12-week training period at three different intensities...
2017: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/28403801/iga-igm-responses-to-gram-negative-bacteria-are-not-associated-with-perinatal-depression-but-with-physio-somatic-symptoms-and-activation-of-the-tryptophan-catabolite-pathway-at-the-end-of-term-and-postnatal-anxiety
#6
Roomruangwong Chutima, Buranee Kanchanatawan, Sunee Sirivichayakul, George Anderson, André F Carvalho, Sebastien Duleu, Michel Geffard, Michael Maes
Evidence has implicated the translocation of commensal Gram-negative bacteria (Gram-B) due to leaky gut in the pathophysiology of depression and physio-somatic symptoms (e.g. fatigue, pain, irritable bowel syndrome, malaise, etc.). In addition, the leaky gut may contribute to immune-inflammatory activation and oxidative stress. This study investigated whether bacterial translocation is associated with perinatal depression and anxiety scores and with prenatal physio-somatic symptoms and immune-inflammatory biomarkers, including the tryptophan catabolite (TRYCAT) pathway...
April 7, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28364692/the-effect-of-three-angiotensin-converting-enzyme-inhibitors-on-kynurenic-acid-production-in-rat-kidney-in-vitro
#7
Izabela Zakrocka, Tomasz Kocki, Waldemar A Turski
BACKGROUND: The renin-angiotensin system (RAS) is commonly known to regulate blood pressure, water and electrolyte homeostasis, however it also exerts paracrine and autocrine actions on the kidney. Angiotensin-converting enzyme inhibitors (ACE-Is), alongside their hypotensive properties, have been shown to decrease kidney function decline in animal models of nephropathy. Glutamate (GLU) is the main stimulatory neurotransmitter in the central nervous system, however its importance in the periphery should also be considered...
January 31, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28338954/meta-analysis-of-cerebrospinal-fluid-cytokine-and-tryptophan-catabolite-alterations-in-psychiatric-patients-comparisons-between-schizophrenia-bipolar-disorder-and-depression
#8
Alexandre K Wang, Brian J Miller
INTRODUCTION: Schizophrenia, bipolar disorder, and major depressive disorder (MDD) have all been associated with immune system dysfunction, including aberrant cerebrospinal fluid (CSF) levels of cytokines and tryptophan catabolites; however, the pattern of alterations has not been compared across disorders. We performed a meta-analysis of CSF cytokine and tryptophan catabolites in patients with these major psychiatric disorders. METHODS: Articles were identified by searching Pub Med, PsycInfo, and Web of Science, and the reference lists of these studies...
March 17, 2017: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/28337634/topical-dura-mater-application-of-cfa-induces-enhanced-expression-of-c-fos-and-glutamate-in-rat-trigeminal-nucleus-caudalis-attenuated-by-kyna-derivate-szr72
#9
M Lukács, K Warfvinge, J Tajti, F Fülöp, J Toldi, L Vécsei, L Edvinsson
BACKGROUND: Migraine is a debilitating neurological disorder where trigeminovascular activation plays a key role. We have previously reported that local application of Complete Freund's Adjuvant (CFA) onto the dura mater caused activation in rat trigeminal ganglion (TG) which was abolished by a systemic administration of kynurenic acid (KYNA) derivate (SZR72). Here, we hypothesize that this activation may extend to the trigeminal complex in the brainstem and is attenuated by treatment with SZR72...
December 2017: Journal of Headache and Pain
https://www.readbyqxmd.com/read/28314892/abnormal-kynurenine-pathway-of-tryptophan-catabolism-in-cardiovascular-diseases
#10
REVIEW
Ping Song, Tharmarajan Ramprasath, Huan Wang, Ming-Hui Zou
Kynurenine pathway (KP) is the primary path of tryptophan (Trp) catabolism in most mammalian cells. The KP generates several bioactive catabolites, such as kynurenine (Kyn), kynurenic acid (KA), 3-hydroxykynurenine (3-HK), xanthurenic acid (XA), and 3-hydroxyanthranilic acid (3-HAA). Increased catabolite concentrations in serum are associated with several cardiovascular diseases (CVD), including heart disease, atherosclerosis, and endothelial dysfunction, as well as their risk factors, including hypertension, diabetes, obesity, and aging...
March 17, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28290151/deficit-schizophrenia-is-characterized-by-defects-in-igm-mediated-responses-to-tryptophan-catabolites-trycats-a-paradigm-shift-towards-defects-in-natural-self-regulatory-immune-responses-coupled-with-mucosa-derived-trycat-pathway-activation
#11
Buranee Kanchanatawan, Sunee Sirivichayakul, Kiat Ruxrungtham, André F Carvalho, Michel Geffard, George Anderson, Michael Maes
Deficit schizophrenia is accompanied by mucosa-associated activation of the tryptophan catabolite (TRYCAT) pathway, as indicated by increased IgA responses to noxious (NOX) TRYCATs, but not regulatory or protective (PRO) TRYCATs, suggesting increased neurotoxic, excitotoxic, inflammatory, and oxidative potential. No previous studies examined IgM-mediated autoimmune responses to the TRYCAT pathway in deficit versus nondeficit schizophrenia. We measured IgM responses to NOX TRYCATs, namely, quinolinic acid (QA), 3-OH-kynurenine (3HK), picolinic acid (PA), and xanthurenic (XA) acid, and PRO TRYCATs, including kynurenic acid (KA) and anthranilic acid (AA), in 40 healthy controls and 40 deficit and 40 nondeficit schizophrenic patients...
March 14, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28285360/kynurenic-acid-downregulates-il-17-1l-23-axis-in-vitro
#12
Sanam Salimi Elizei, Malihe-Sadat Poormasjedi-Meibod, Xia Wang, Maryam Kheirandish, Aziz Ghahary
Exploring the function of interleukin (IL) 17 and related cytokine interactions have been proven useful toward understanding the role of inflammation in autoimmune diseases. Production of the inflammatory cytokine IL-23 by dendritic cells (DC's) has been shown to promote IL-17 expression by Th17 cells. It is well established that Th17 cells play an important role in several autoimmune diseases including psoriasis and alopecia. Our recent investigations have suggested that Kynurenine-rich environment can shift a pro-inflammatory response to an anti-inflammatory response, as is the case in the presence of the enzyme Indoleamine 2,3 dioxygenase (IDO), the rate-limiting enzyme in tryptophan degradation and Kynurenine (Kyn) production...
March 11, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28280461/glutamate-and-opioid-antagonists-modulate-dopamine-levels-evoked-by-innately-attractive-male-chemosignals-in-the-nucleus-accumbens-of-female-rats
#13
María-José Sánchez-Catalán, Alejandro Orrico, Lucía Hipólito, Teodoro Zornoza, Ana Polache, Enrique Lanuza, Fernando Martínez-García, Luis Granero, Carmen Agustín-Pavón
Sexual chemosignals detected by vomeronasal and olfactory systems mediate intersexual attraction in rodents, and act as a natural reinforcer to them. The mesolimbic pathway processes natural rewards, and the nucleus accumbens receives olfactory information via glutamatergic projections from the amygdala. Thus, the aim of this study was to investigate the involvement of the mesolimbic pathway in the attraction toward sexual chemosignals. Our data show that female rats with no previous experience with males or their chemosignals display an innate preference for male-soiled bedding...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28275903/correlations-of-kynurenic-acid-3-hydroxykynurenine-sil-2r-ifn-%C3%AE-and-il-4-with-clinical-symptoms-during-acute-relapse-of-schizophrenia
#14
Kinga Szymona, Barbara Zdzisińska, Hanna Karakuła-Juchnowicz, Tomasz Kocki, Martyna Kandefer-Szerszeń, Marta Flis, Wojciech Rosa, Ewa M Urbańska
Several lines of evidence suggest that up-regulation of immune response and alterations of kynurenine pathway function are involved in pathogenesis of schizophrenia. Correlations among clinical status (using PANNS, SANS and SAPS scales) and blood levels of kynurenic acid (KYNA), 3-hydroxykynurenine (3-HK) and levels of selected immunoactive molecules, soluble interleukin-2 receptor (sIL-2R), interferon-α (IFN-α) and IL-4 were analyzed in 51 chronic schizophrenia patients during acute relapse, after four weeks of therapy and at remission...
March 8, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28258445/physio-somatic-symptoms-in-schizophrenia-association-with-depression-anxiety-neurocognitive-deficits-and-the-tryptophan-catabolite-pathway
#15
Buranee Kanchanatawan, Sunee Sirivichayakul, Supaksorn Thika, Kiat Ruxrungtham, André F Carvalho, Michel Geffard, George Anderson, Cristiano Noto, Rada Ivanova, Michael Maes
To investigate the frequency of physio-somatic symptoms (PS) symptoms in schizophrenia and their relation to positive, negative and affective symptoms; neurocognitive deficits and impairments in the tryptophan catabolite (TRYCAT) pathway. Eighty four patients with schizophrenia and 40 healthy controls were assessed using the 12 item Fibromyalgia and Chronic Fatigue Syndrome Rating scale (FF) and scales for negative and positive symptoms, depression and anxiety. Cognitive functioning was tested using the Cambridge Neuropsychological Test Automated Battery (CANTAB)...
March 3, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28255983/vasopressin-v1a-receptors-mediate-the-hypertensive-effects-of-pyr-1-apelin-13-in-the-rat-rostral-ventrolateral-medulla
#16
Philip R Griffiths, Stephen J Lolait, Louise E Harris, Julian Fr Paton, Anne-Marie O'Carroll
Apelin is a ubiquitous peptide that can elevate arterial blood pressure (ABP) yet understanding of the mechanisms involved remain incomplete. Bilateral microinjection of [Pyr(1) ]apelin-13 into the rostral ventrolateral medulla (RVLM), a major source of sympathoexcitatory neurones, increases ABP and sympathetic nerve activity. We sought to investigate the potential involvement of neurotransmitter systems through which the apelin pressor response may occur within the RVLM. Adult male Wistar rats were anaesthetised and ABP was monitored via a femoral arterial catheter...
March 2, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28250153/microinjection-of-kynurenic-acid-in-the-rostral-nucleus-of-the-tractus-solitarius-disrupts-spatiotemporal-aspects-of-mechanically-induced-tracheobronchial-cough
#17
Ivan Poliacek, Teresa Pitts, Melanie J Rose, Paul W Davenport, Michal Simera, Marcel Veternik, Zuzana Kotmanova, Donald C Bolser
The importance of neurons in the solitary tract nucleus (NTS) in the production of coughing was tested by microinjections of the non-specific glutamate receptor antagonist kynurenic acid (kyn; 100 mM in artificial cerebrospinal fluid) in 15 adult spontaneously breathing anesthetized cats. Repetitive coughing was elicited by mechanical stimulation of the intrathoracic airway. Electromyograms (EMG) were recorded from inspiratory parasternal and expiratory transversus abdominis muscles (ABD). Bilateral microinjections of kyn into the NTS rostral to obex (55±4 nl total in two locations; n=6 or 110±4 nl total in four locations; n=5), primarily the ventrolateral subnucleus, reduced cough number and expiratory cough efforts (amplitudes of ABD EMG and maxima of esophageal pressure) compared to control...
March 1, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28245765/kynurenines-and-pacap-in-migraine-medicinal-chemistry-and-pathogenetic-aspects
#18
János Tajti, Délia Szok, Gábor Nagy-Grócz, Bernadett Tuka, Anna Petrovics-Balog, József Toldi, László Vécsei
BACKGROUND: Migraine is a highly disabling neurovascular primary headache disorder, with its exact pathomechanism being still unrevealed. The current leading hypotheses are based on the sensitization and activation of the trigeminovascular system. OBJECTIVE: To review the literature with focus on the effects of kynurenines (L-kynurenine and kynurenic acid) and pituitary adenylate cyclase-activating polypeptide on the regulation of the trigeminovascular system. METHOD: A literature search was conducted to identify preclinical and clinical publications (198 references) by using the keywords 'kynurenines', 'pituitary adenylate cyclase-activating polypeptide', and 'migraine' in the database of MEDLINE/PubMed up to 10 September 2016for topical review...
February 27, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28243208/high-kynurenine-a-tryptophan-metabolite-predicts-remission-in-patients-with-major-depression-to-add-on-treatment-with-celecoxib
#19
Daniela Krause, Aye-Mu Myint, Christine Schuett, Richard Musil, Sandra Dehning, Anja Cerovecki, Michael Riedel, Volker Arolt, Markus J Schwarz, Norbert Müller
BACKGROUND: Signs of an inflammatory process have been described in major depression. METHODS: In a double-blind, randomized study of celecoxib or placebo add-on to reboxetine in 40 depressed patients, celecoxib treatment has beneficial effects. In order to evaluate the tryptophan/kynurenine metabolism and to identify predictors for remission, tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), and quinolinic acid (QUIN) were estimated in the serum of 32 patients before and after treatment and in a group of 20 healthy controls...
2017: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/28241496/the-role-of-sarcosine-uracil-and-kynurenic-acid-metabolism-in-urine-for-diagnosis-and-progression-monitoring-of-prostate-cancer
#20
Georgios Gkotsos, Christina Virgiliou, Ioanna Lagoudaki, Chrysanthi Sardeli, Nikolaos Raikos, Georgios Theodoridis, Georgios Dimitriadis
The aim of this pilot study is to evaluate sarcosine, uracil, and kynurenic acid in urine as potential biomarkers in prostate cancer detection and progression monitoring. Sarcosine, uracil, and kynurenic acid were measured in urine samples of 32 prostate cancer patients prior to radical prostatectomy, 101 patients with increased prostate-specific antigen prior to ultrasonographically-guided prostatic biopsy collected before and after prostatic massage, and 15 healthy volunteers (controls). The results were related to histopathologic data, Gleason score, and PSA (Prostate Specific Antigen)...
February 23, 2017: Metabolites
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