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Kynurenine depression

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https://www.readbyqxmd.com/read/28155213/intracerebroventricular-administration-of-streptozotocin-as-an-experimental-approach-to-depression-evidence-for-the-involvement-of-proinflammatory-cytokines-and-indoleamine-2-3-dioxygenase
#1
Leandro Cattelan Souza, Cristiano R Jesse, Marcelo Gomes de Gomes, Cristini Escobar Viana, Etiara Mattos, Neici Cáceres Silva, Silvana Peterini Boeira
There is a lack of information about the molecular events underlying the depressive-like effect of an intracerebroventricular injection of streptozotocin (ICV-STZ) in mice. Elevated activity of the tryptophan-degrading enzyme indoleamine-2,3-dioxygenase (IDO) has been proposed to mediate depression in inflammatory disorders. In this study, we report that ICV-STZ activates IDO in the hippocampus of mice and culminates in depressive-like behaviors, measured by an increased duration in immobility time in the forced swimming test and decreased total time of grooming in the splash test...
February 2, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28138019/involvement-of-host-defense-mechanisms-against-toxoplasma-gondii-infection-in-anhedonic-and-despair-like-behaviors-in-mice
#2
Motamed E Mahmoud, Ragab Fereig, Yoshifumi Nishikawa
Toxoplasma gondii is a pathogen relevant to psychiatric disorders. We recently showed that reactivation of chronic T. gondii induced depressive-like behaviors in mice. Further, it has been hypothesized that depression-like behaviors are mediated via a host defense mechanism against invading pathogens; proximate mechanisms of this behavioral hypothesis remain unclear. In the present study, we investigate the contribution of indoleamine 2, 3-dioxygenase (IDO), inflammation and interferon-gamma (IFN-γ) on anhedonic- and despair-related behaviors in T...
January 30, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28112061/inflammation-and-depression-a-causal-or-coincidental-link-to-the-pathophysiology
#3
Brian E Leonard
This review summarises the evidence that chronic low grade inflammation triggers changes that contribute to the mental and physical ill health of patients with major depression. Inflammation, and the activation of the hypothalamic pituitary axis by stress, are normal components of the stress response but when stress is prolonged and the endocrine and immune system become chronic resulting in the activation of the peripheral macrophages, the central microglia and hypercortisolemia, the neuronal networks are damaged and become dysfunctional...
January 23, 2017: Acta Neuropsychiatrica
https://www.readbyqxmd.com/read/28078987/role-of-proinflammatory-cytokines-in-dopaminergic-system-disturbances-implications-for-anhedonic-features-of-mdd
#4
Zihang Pan, Joshua D Rosenblat, Walter Swardfager, Roger S McIntyre
Anhedonia, characterized by a loss of interest and/or pleasure in previously enjoyable activities, is an important diagnostic criterion of Major Depressive Disorder (MDD). Converging evidence implicates a behaviouralcausal relationship between proinflammatory cytokines and disturbances that characterize anhedonia in the context of MDD. Additionally, anhedonia has been implicated in disturbances of key central dopaminergic modulatory pathways. Emerging research into the roles of tetrahydrobiopterin, a cytokine-targeted co-enzyme in the synthesis of dopamine, and kynurenine, a product of inflammation-sensitive breakdown of tryptophan via indoleamine 2, 3-dioxygenase, have shed new light into the role of inflammation in mediating anhedonic behaviours...
January 11, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28065794/adjuvant-quercetin-therapy-for-combined-treatment-of-epilepsy-and-comorbid-depression
#5
Tanveer Singh, Taranjot Kaur, Rajesh Kumar Goel
Epilepsy is one of the major neurological disorders frequently associated with psychiatric disorders such as depression. The predisposition of tryptophan metabolism towards kynurenine pathway has been reported as one of the plausible reasons for association of depression in epilepsy. Hence, this study was envisaged to evaluate the dose dependent inhibition of indoleamine 2,3-dioxygenase (IDO) enzyme employing quercetin (screened employing in vitro method) with levetiracetam for combined management of epilepsy and comorbid depression...
January 5, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28058465/fish-oil-supplementation-attenuates-neuroinflammation-and-alleviates-depressive-like-behavior-in-rats-submitted-to-repeated-lipopolysaccharide
#6
Ruili Dang, Xueyuan Zhou, Mimi Tang, Pengfei Xu, Xiaoxue Gong, Yuanyuan Liu, Hongxiao Jiao, Pei Jiang
PURPOSE: Depression is frequently associated with inflammation, whereas omega-3 polyunsaturated fatty acids (PUFAs) primarily found in fish oil possess anti-inflammatory properties. Although converging studies suggest an antidepressant effect of PUFAs, there is limited evidence directly linking the neuro-immune modulating features of PUFAs to the antidepressant actions. METHODS: Therefore, we assessed the effects of fish oil (FO) supplementation on behavioral changes, inflammatory cytokine expression and oxidative reactions in frontal cortex and hippocampus of rats following repeated peripheral immune challenge by lipopolysaccharide (LPS) for 2 weeks (500 μg/kg every other day)...
January 5, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/27923157/adjuvant-neuronal-nitric-oxide-synthase-inhibition-for-combined-treatment-of-epilepsy-and-comorbid-depression
#7
Tanveer Singh, Rajesh Kumar Goel
BACKGROUND: Elevated nitric oxide (NO) levels in the brain have been apparently associated with depression in kindled animals. Owing to the major role of neuronal nitric oxide synthase (nNOS) in brain and ineffectiveness of antiepileptic drugs (AEDs) in restoring nitrosative stress, the present study was envisaged to evaluate the adjuvant nNOS inhibitor, 7-nitroindazole (7-NI) with valproic acid for combined treatment of epilepsy and associated depression. METHODS: Pentylenetetrazole kindled animals associated with depression were treated with vehicle, valproate (300mg/kg/day ip), valproate with 7-NI (10mg/kg; 20mg/kg; 40mg/kg)/day ip and 7-NI (40mg/kg/day ip) for 15days...
February 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/27876634/individual-and-interactive-sex-specific-effects-of-acute-restraint-and-systemic-ifn-%C3%AE-treatment-on-neurochemistry
#8
Darcy Litteljohn, Chris Rudyk, Sara Razmjou, Zach Dwyer, Shuaib Syed, Shawn Hayley
Compelling evidence supports the involvement of the pro-inflammatory cytokines, IL-6, IFN-α and TNF-α in depression and related stress-associated pathologies. A role has also been suggested for the Th1-type cytokine, IFN-γ, with most mechanistic accounts focusing on the cytokine's capacity to induce indoleamine 2,3-dioxygenase (IDO), leading to diminished tryptophan and the generation of kynurenine metabolites. Beyond these IDO-dependent routes, there is surprisingly little evidence directly linking IFN-γ to alterations of brain regional monoamine activity and HPA axis functioning...
November 19, 2016: Neurochemistry International
https://www.readbyqxmd.com/read/27832762/tryptophan-metabolism-its-relation-to-inflammation-and-stress-markers-and-association-with-psychological-and-cognitive-functioning-tasmanian-chronic-kidney-disease-pilot-study
#9
Naama Karu, Charlotte McKercher, David S Nichols, Noel Davies, Robert A Shellie, Emily F Hilder, Matthew D Jose
BACKGROUND: Adults with chronic kidney disease (CKD) exhibit alterations in tryptophan metabolism, mainly via the kynurenine pathway, due to higher enzymatic activity induced mainly by inflammation. Indoles produced by gut-microflora are another group of tryptophan metabolites related to inflammation and conditions accompanying CKD. Disruptions in tryptophan metabolism have been associated with various neurological and psychological disorders. A high proportion of CKD patients self-report symptoms of depression and/or anxiety and decline in cognitive functioning...
November 10, 2016: BMC Nephrology
https://www.readbyqxmd.com/read/27830572/inflammation-associated-co-morbidity-between-depression-and-cardiovascular-disease
#10
Angelos Halaris
Morbidity and mortality of cardiovascular disease (CVD) is exceedingly high worldwide. Depressive illness is a serious psychiatric illness that afflicts a significant portion of the world population. Epidemiological studies have confirmed the high co-morbidity between these two disease entities. The co-morbidity is bidirectional and the mechanisms responsible for it are complex and multifaceted. In addition to genetic, biological systems, psychosocial, and behavioral factors that are involved include the central and autonomic nervous systems, the neuroendocrine, immune, and the vascular and hematologic systems...
2017: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/27828964/chronic-treatment-with-the-ido1-inhibitor-1-methyl-d-tryptophan-minimizes-the-behavioural-and-biochemical-abnormalities-induced-by-unpredictable-chronic-mild-stress-in-mice-comparison-with-fluoxetine
#11
Anthony Laugeray, Jean-Marie Launay, Jacques Callebert, Oguz Mutlu, Gilles J Guillemin, Catherine Belzung, Pascal R Barone
We demonstrated that confronting mice to the Unpredictable Chronic Mild Stress (UCMS) procedure-a validated model of stress-induced depression-results in behavioural alterations and biochemical changes in the kynurenine pathway (KP), suspected to modify the glutamatergic neurotransmission through the imbalance between downstream metabolites such as 3-hydroxykynurenine, quinolinic and kynurenic acids. We showed that daily treatment with the IDO1 inhibitor 1-methyl-D-tryptophan partially rescues UCMS-induced KP alterations as does the antidepressant fluoxetine...
2016: PloS One
https://www.readbyqxmd.com/read/27818124/chrysin-promotes-attenuation-of-depressive-like-behavior-and-hippocampal-dysfunction-resulting-from-olfactory-bulbectomy-in-mice
#12
Carlos Borges Filho, Cristiano Ricardo Jesse, Franciele Donato, Lucian Del Fabbro, Marcelo Gomes de Gomes, André Tiago Rossito Goes, Leandro Cattelan Souza, Silvana Peterini Boeira
Chrysin is a natural flavonoid which is found in bee propolis, honey and various plants, and antidepressant-like effect of chrysin in chronically stressed mice was previously demonstrated by our group. In this work, we investigated the action of chrysin treatment (5 or 20 mg/kg) for 14 days in the depressant-like behavior and in the hippocampal dysfunction induced by olfactory bulbectomy (OB), an animal model of agitated depression. Results demonstrated that OB occasioned a depressant-like behavior in the splash test, open field test and forced swimming test...
December 25, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/27812290/tryptophan-metabolism-and-its-relationship-with-depression-and-cognitive-impairment-among-hiv-infected-individuals
#13
Michael R Keegan, Seetharamaiah Chittiprol, Scott L Letendre, Alan Winston, Dietmar Fuchs, Adriano Boasso, Jennifer Iudicello, Ronald J Ellis
OBJECTIVE: Cognitive impairment (CI) and major depressive disorder (MDD) remain prevalent in treated HIV-1 disease; however, the pathogenesis remains elusive. A possible contributing mechanism is immune-mediated degradation of tryptophan (TRP) via the kynurenine (KYN) pathway, resulting in decreased production of serotonin and accumulation of TRP degradation products. We explored the association of these biochemical pathways and their relationship with CI and MDD in HIV-positive (HIV+) individuals...
2016: International Journal of Tryptophan Research: IJTR
https://www.readbyqxmd.com/read/27799931/immunomodulatory-factors-galectin-9-and-interferon-gamma-synergize-to-induce-expression-of-rate-limiting-enzymes-of-the-kynurenine-pathway-in-the-mouse-hippocampus
#14
Alexandra K Brooks, Marcus A Lawson, Jennifer L Rytych, Kevin C Yu, Tiffany M Janda, Andrew J Steelman, Robert H McCusker
Elevated levels of circulating pro-inflammatory cytokines are associated with symptomology of several psychiatric disorders, notably major depressive disorder. Symptomology has been linked to inflammation/cytokine-dependent induction of the Kynurenine Pathway. Galectins, like pro-inflammatory cytokines, play a role in neuroinflammation and the pathogenesis of several neurological disorders but without a clearly defined mechanism of action. Their involvement in the Kynurenine Pathway has not been investigated...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27778340/maternal-protein-restriction-during-gestation-and-lactation-in-the-rat-results-in-increased-brain-levels-of-kynurenine-and-kynurenic-acid-in-their-adult-offspring
#15
Paula Honório de Melo Martimiano, André de Sa Braga Oliveira, Véronique Ferchaud-Roucher, Mikaël Croyal, Audrey Aguesse, Isabelle Grit, Khadija Ouguerram, Sandra Lopes de Souza, Bertrand Kaeffer, Francisco Bolaños-Jiménez
Early malnutrition is a risk factor for depression and schizophrenia. Since the offspring of malnourished dams exhibit increased brain levels of serotonin (5-HT), a tryptophan-derived neurotransmitter involved in the pathophysiology of these mental disorders, it is believed that the deleterious effects of early malnutrition on brain function are due in large part to altered serotoninergic neurotransmission resulting from impaired tryptophan (Trp) metabolism. However, tryptophan is also metabolized through the kynurenine (KYN) pathway yielding several neuroactive compounds including kynurenic (KA), quinolinic (QA) and xanthurenic (XA) acids...
January 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27754481/neurotoxic-kynurenine-metabolism-is-increased-in-the-dorsal-hippocampus-and-drives-distinct-depressive-behaviors-during-inflammation
#16
J M Parrott, L Redus, D Santana-Coelho, J Morales, X Gao, J C O'Connor
The kynurenine pathway of tryptophan metabolism has an important role in mediating the behavioral effects of inflammation, which has implications in understanding neuropsychiatric comorbidity and for the development of novel therapies. Inhibition of the rate-limiting enzyme, indoleamine 2,3-dioxygenase (IDO), prevents the development of many of these inflammation-induced preclinical behaviors. However, dysregulation in the balance of downstream metabolism, where neuroactive kynurenines are generated, is hypothesized to be a functionally important pathogenic feature of inflammation-induced depression...
October 18, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27730347/targeting-oxidative-stress-cytokines-and-serotonin-interactions-via-indoleamine-2-3-dioxygenase-by-coenzyme-q10-role-in-suppressing-depressive-like-behavior-in-rats
#17
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
https://www.readbyqxmd.com/read/27693848/kynurenine-3-monooxygenase-is-implicated-in-antidepressants-responsive-depressive-like-behaviors-and-monoaminergic-dysfunctions
#18
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
https://www.readbyqxmd.com/read/27640517/stress-the-autonomic-nervous-system-and-the-immune-kynurenine-pathway-in-the-etiology-of-depression
#19
REVIEW
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
https://www.readbyqxmd.com/read/27619930/kynurenine-pathway-and-white-matter-microstructure-in-bipolar-disorder
#20
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
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