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Kynurenine depression

Sally A Abuelezz, Nevien Hendawy, Yosra Magdy
Depression is a major health problem in which oxidative stress and inflammation are inextricably connected in its pathophysiology. Coenzyme Q10 (CoQ10) is an important anti-oxidant compound with anti-inflammatory and neuro-protective properties. This study was designed to investigate the hypothesis that CoQ10 by its anti-oxidant and anti-inflammatory potentials can alleviate depressive- like behavior by restoring the balance of the tryptophan catabolites kynurenine/serotonin toward the serotonin pathway by down-regulation of hippocampal indoleamine 2,3-dioxygenase 1 (IDO-1)...
October 11, 2016: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
Tomoyuki Tashiro, Yuki Murakami, Akihiro Mouri, Yukio Imamura, Toshitaka Nabeshima, Yasuko Yamamoto, Kuniaki Saito
l-Tryptophan (TRP) is metabolized via serotonin and kynurenine pathways (KP). Several studies have demonstrated that abnormality of both pathways is involved in the pathogenesis of major depressive disorder (MDD). Kynurenine 3-monooxygenase (KMO), a pivotal enzyme in the KP, has been suggested to play major roles in physiological and pathological events mediated by bioactive kynurenine metabolites. In this study, we investigated the role of KMO in the emotional and cognitive functions by using KMO knockout (KO) mice...
September 28, 2016: Behavioural Brain Research
Eunsoo Won, Yong-Ku Kim
The autonomic nervous system is one of the major neural pathways activated by stress. In situations that are often associated with chronic stress, such as major depressive disorder, the sympathetic nervous system can be continuously activated without the normal counteraction of the parasympathetic nervous system. As a result, the immune system can be activated with increased levels of proinflammatory cytokines. These inflammatory conditions have been repeatedly observed in depression. In the search for the mechanism by which the immune system might contribute to depression, the enhanced activity of indoleamine 2,3- dioxygenase by pro-inflammatory cytokines has been suggested to play an important role...
2016: Current Neuropharmacology
Sara Poletti, Aye Mu Myint, Gregor Schüetze, Irene Bollettini, Elena Mazza, Doris Grillitsch, Clara Locatelli, Markus Schwarz, Cristina Colombo, Francesco Benedetti
Decreased availability of serotonin in the central nervous system has been suggested to be a central factor in the pathogenesis of depression. Activation of indoleamine 2-3 dioxygenase following a pro-inflammatory state could reduce the amount of tryptophan converted to serotonin and increase the production of tryptophan catabolites such as kynurenic acid, an antagonist of ionotropic excitatory aminoacid receptors, whose levels are reduced in bipolar disorder. Abnormalities in white matter (WM) integrity have been widely reported in BD...
September 12, 2016: European Archives of Psychiatry and Clinical Neuroscience
Carlos Borges Filho, Cristiano Ricardo Jesse, Franciele Donato, Lucian Del Fabbro, Marcelo Gomes de Gomes, André Tiago Rossito Goes, Leandro Cattelan Souza, Renata Giacomeli, Michelle Antunes, Cristiane Luchese, Silvane Souza Roman, Silvana Peterini Boeira
Chrysin is a flavonoid which is found in bee propolis, honey and various plants. Antidepressant-like effect of chrysin in chronically stressed mice was previously demonstrated by our group. Conversely, neurochemical factors associated with this effect require further investigations. Thus, we investigated the possible involvement of pro-inflammatory cytokines, kynurenine pathway (KP), 5-hydroxytryptamine (5-HT) metabolism and caspases activities in the effect of chrysin in mice exposed to unpredictable chronic stress (UCS)...
September 5, 2016: European Journal of Pharmacology
George Anderson, M Seo, M Berk, A F Carvalho, M Maes
BACKGROUND: Increased gut permeability (leaky gut) and alterations in gut microbiota are now widely accepted as relevant to the etiology, course and treatment of many neuropsychiatric disorders, including Parkinson disease (PD). Although a wide array of data on the biological underpinnings of PD has not yet been linked to such gut-associated changes, increased gut permeability and dysregulated microbiota alter many pathways germane to PD. METHODS: In this article we review and integrate these wider biological changes in PD, including increased oxidative and nitrosative stress, immune-inflammatory processes, tryptophan catabolites and alterations in serotoninergic and melatoninergic pathways...
September 6, 2016: Current Pharmaceutical Design
Li-Jun Hu, Xiao-Fang Li, Jin-Qing Hu, Xiao-Jia Ni, Hao-Yang Lu, Jia-Jia Wang, Xiang-Ning Huang, Chao-Xian Lin, De-Wei Shang, Yu-Guan Wen
The kynurenine pathway, in which tryptophan is metabolized to kynurenine and kynurenic acid, has been linked to depression. A rapid and highly reproducible liquid-chromatography-tandem mass spectrometry (LC-MS/MS) method were established for determining tryptophan, kynurenine and kynurenic acid in human serum. Biological samples were precipitated with methanol before separation on an Agilent Eclipse XDB-C18. The stable-isotope-labeled internal standards (kynurenine-(13)C4 (15)N and kynurenic acid-d5) were used for quantification...
September 1, 2016: Journal of Analytical Toxicology
Proteesh Rana, Amit K Sharma, Smita Jain, Pravin Deshmukh, S K Bhattacharya, B D Banerjee, Pramod K Mediratta
BACKGROUND: The inflammatory response system has been implicated in the pathophysiology of major depression. The pro-inflammatory cytokines like interferon-γ induce the enzyme indoleamine-2,3-dioxygenase (IDO) of the kynurenine pathway of tryptophan metabolism. The induction of IDO reduces the availability of tryptophan for serotonin synthesis. Furthermore, the metabolites of kynurenine pathway have neurotoxic property, which along with decreased serotonin may account for depression-like illness...
August 5, 2016: Journal of Basic and Clinical Physiology and Pharmacology
Guang-Fen Zhang, Jing Wang, Jin-Feng Han, Jie Guo, Ze-Min Xie, Wei Pan, Jian-Jun Yang, Kang-Jian Sun
Both chronic pain and depression are debilitating diseases, which often coexist in clinic. However, current analgesics and antidepressants exhibit limited efficacy for this comorbidity. The present study aimed to investigate the effect of ketamine on the comorbidity of inflammatory pain and consequent depression-like behaviors in a rat model established by intraplantar administration of complete Freunds adjuvant (CFA). The mechanical withdrawal threshold, thermal withdrawal latency, open field test, forced swimming test, and sucrose preference test were evaluated after the CFA injection and ketamine treatment...
September 19, 2016: Neuroscience Letters
John R Kelly, Yuliya Borre, Ciaran O' Brien, Elaine Patterson, Sahar El Aidy, Jennifer Deane, Paul J Kennedy, Sasja Beers, Karen Scott, Gerard Moloney, Alan E Hoban, Lucinda Scott, Patrick Fitzgerald, Paul Ross, Catherine Stanton, Gerard Clarke, John F Cryan, Timothy G Dinan
The gut microbiota interacts with the host via neuroimmune, neuroendocrine and neural pathways. These pathways are components of the brain-gut-microbiota axis and preclinical evidence suggests that the microbiota can recruit this bidirectional communication system to modulate brain development, function and behaviour. The pathophysiology of depression involves neuroimmune-neuroendocrine dysregulation. However, the extent to which changes in gut microbiota composition and function mediate the dysregulation of these pathways is unknown...
November 2016: Journal of Psychiatric Research
L Brundin, C M Sellgren, C K Lim, J Grit, E Pålsson, M Landén, M Samuelsson, K Lundgren, P Brundin, D Fuchs, T T Postolache, L Traskman-Bendz, G J Guillemin, S Erhardt
Emerging evidence suggests that inflammation has a key role in depression and suicidal behavior. The kynurenine pathway is involved in neuroinflammation and regulates glutamate neurotransmission. In the cerebrospinal fluid (CSF) of suicidal patients, levels of inflammatory cytokines and the kynurenine metabolite quinolinic acid (QUIN), an N-methyl-d-aspartate receptor agonist, are increased. The enzyme amino-β-carboxymuconate-semialdehyde-decarboxylase (ACMSD) limits QUIN formation by competitive production of the neuroprotective metabolite picolinic acid (PIC)...
2016: Translational Psychiatry
April C L Bostian, Robert L Eoff
Metabolism of the essential amino acid L-tryptophan (TRP) is implicated in a number of neurological conditions including depression, neurodegenerative diseases, and cancer. The TRP catabolite kynurenine (KYN) has recently emerged as an important neuroactive factor in brain tumor pathogenesis, with additional studies implicating KYN in other types of cancer. Often highlighted as a modulator of the immune response and a contributor to immune escape for malignant tumors, it is well-known that KYN has effects on the production of the coenzyme nicotinamide adenine dinucleotide (NAD(+)), which can have a direct impact on DNA repair, replication, cell division, redox signaling, and mitochondrial function...
September 19, 2016: Chemical Research in Toxicology
Yuki Murakami, Takaaki Ishibashi, Eiichi Tomita, Yukio Imamura, Tomoyuki Tashiro, Kanitta Watcharanurak, Makiya Nishikawa, Yuki Takahashi, Yoshinobu Takakura, Satoko Mitani, Hidetsugu Fujigaki, Yoshiji Ohta, Hisako Kubo, Takayoshi Mamiya, Toshitaka Nabeshima, Hyoung-Chun Kim, Yasuko Yamamoto, Kuniaki Saito
Depression is known to occur frequently in chronic hepatitis C viral (HCV) patients receiving interferon (IFN)-α therapy. In this study, we investigated whether indoleamine 2,3-dioxygenase1 (IDO1)-mediated tryptophan (TRP) metabolism plays a critical role in depression occurring as a side effect of IFN-α therapy. Increases in serum kynurenine (KYN) and 3-hydroxykynurenine (3-HK) concentrations and in the ratios of KYN/TRP and 3-HK/kynurenic acid (KA) were much larger in depressive HCV patients than in non-depressed patients following therapy...
2016: Scientific Reports
Chutima Roomruangwong, Buranee Kanchanatawan, André F Carvalho, Sunee Sirivichayakul, Sebastien Dulue, Michel Geffard, Michael Maes
OBJECTIVES: The aim of the present study is to delineate the associations between body image dissatisfaction in pregnant women and immune-inflammatory biomarkers, i.e. C-reactive protein (CRP), zinc and IgA/IgM responses to tryptophan and TRYCATs. METHODS: We assessed 49 pregnant and 24 non-pregnant females and assessed Body Image Satisfaction (BIS) scores at the end of term (T1), 2-4 days (T2) and 4-6 weeks (T3) after delivery. Subjects were divided in those with a lowered BIS score (≤ 3) versus those with a higher score...
July 18, 2016: World Journal of Biological Psychiatry
Xi-Cong Liu, Sophie Erhardt, Michel Goiny, Göran Engberg, Aleksander A Mathé
OBJECTIVE: There is a growing interest in the role of kynurenine pathway and tryptophan metabolites in the pathophysiology of depression. In the present study, the metabolism of tryptophan along the kynurenine pathway was analysed in a rat model of depression. METHODS: Kynurenic acid (KYNA) and 3-hydroxykynurenine (3-HK) were measured by high-performance liquid chromatography (HPLC) in prefrontal cortex (PFC) and frontal cortex (FC) in a rat model of depression, the Flinders Sensitive Line (FSL) and their controls, the Flinders Resistant Line (FRL) rats...
July 13, 2016: Acta Neuropsychiatrica
P J Kennedy, J F Cryan, T G Dinan, G Clarke
It has become increasingly clear that the gut microbiota influences not only gastrointestinal physiology but also central nervous system (CNS) function by modulating signalling pathways of the microbiota-gut-brain axis. Understanding the neurobiological mechanisms underpinning the influence exerted by the gut microbiota on brain function and behaviour has become a key research priority. Microbial regulation of tryptophan metabolism has become a focal point in this regard, with dual emphasis on the regulation of serotonin synthesis and the control of kynurenine pathway metabolism...
July 5, 2016: Neuropharmacology
Stephani Velasquez, Jay Rappaport
No abstract text is available yet for this article.
July 1, 2016: Biological Psychiatry
Jaya Thomas, R Khanam, Divya Vohora
Agomelatine is a novel antidepressant with agonistic actions at melatonergic (MT1 and MT2 receptors) and antagonistic actions at 5HT-2C receptors. Venlafaxine, a serotonin norepinephrine reuptake inhibitor, is a widely prescribed drug in depression. The present study evaluated the low dose combinations of venlafaxine and agomelatine in chronic forced swim test (chronic FST) and tail suspension test (TST) in mice. Further, the effect of above drugs and their combination was evaluated on serum pro-inflammatory cytokines and hippocampal indole amine 2, 3 dioxygenase (IDO) activity by calculating the ratios of kynurenine/tryptophan (KYN/TRP) and serotonin/tryptophan (5HT/TRP)...
October 2016: Neurochemistry International
Barbara Strasser, Barbara Sperner-Unterweger, Dietmar Fuchs, Johanna M Gostner
Metabolic parameters have a direct role in the regulation of immune cell function. Thereby the inflammation-induced metabolism of aromatic amino acids, most importantly of tryptophan and phenylalanine, plays a central role. In addition, neuropsychiatric conditions that go along with disorders that are characterized by acute or chronic inflammation, such as the development of depression, decreased quality of life or cognitive impairments, are connected to disturbed amino acid and subsequent neurotransmitter metabolism...
June 9, 2016: Current Topics in Behavioral Neurosciences
Yujin Guo, Hualin Cai, Lei Chen, Donglou Liang, Ranyao Yang, Ruili Dang, Pei Jiang
Peripheral administration of lipopolysaccharide (LPS) can induce the rodents to a depression-like state accompanied with remarkable changes of neurotransmitter systems. In this study, the effect of an intraperitoneal LPS injection (3mg/kg) on the concentrations of neurotransmitters was investigated by in vivo microdialysis in rat hippocampus. To further explore dysregulation pattern of the neurotransmitters following continuous inflammatory process, we then analyzed the neurotransmitters in the hippocampus of rats after 2-week LPS exposure (500μg/kg every other day)...
June 15, 2016: Journal of Neuroimmunology
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