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Interferon-induced depression

Francisco S Barreto, Adriano J M Chaves Filho, Márcia C C R de Araújo, Manoel O de Moraes, Maria E A de Moraes, Michael Maes, David F de Lucena, Danielle S Macedo
Both depression and cancer are related to a dysregulation of inflammatory and immune pathways. Indeed, depression is associated with increased expression of interferon-γ, interleukin-1β, and tumor necrosis factor α (TNF-α). In contrast, reductions of the activity of major histocompatibility complex protein molecules - class I and class II and natural killer cells are also observed. Similarly, cancers present elevated levels of TNF-α, reduced major histocompatibility complex class I and II, and natural killer cells...
April 2018: Behavioural Pharmacology
Weihui Gou, Zhen Zhang, Chunfeng Yang, Yumei Li
Macrophage polarization plays a crucial role in regulating myocardial inflammation and injuries of coxsackievirus B3 (CVB3)-induced viral myocarditis (VM). It has been reported that miR-223 is a potent regulator of inflammatory responses that involved in macrophage polarization. However, the functional roles of miR-223 in CVB3-induced VM still remain unknown. Here, we found that miR-223 expression was significantly down-regulated in heart tissues and heart-infiltrating macrophages of CVB3-infected mice. Up-regulation of miR-223 in vivo protected the mice against CVB3-induced myocardial injuries characterized by the increased body weight and survival, enhanced left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), relieved inflammation, depressed creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH) and aspartate transaminase (AST) levels, reduced production of interferon (IFN)-γ, interleukin (IL)-6 as well as increased IL-10...
March 7, 2018: Experimental Cell Research
Tina Markus, David Ley, Stefan R Hansson, Tadeusz Wieloch, Karsten Ruscher
BACKGROUND: Labor subjects the fetus to an hypoxic episode and concomitant adrenomodullary catecholamine surge that may provide protection against the hypoxic insult. The beta1-adrenergic agonist dobutamine protects against hypoxia/aglycemia induced neuronal damage. We aimed to identify the associated protective biological processes involved. RESULTS: Hippocampal slices from 6 days old mice showed significant changes of gene expression comparing slices with or without dobutamine (50 mM) in the following two experimental paradigms: (1) control conditions versus lipopolysacharide (LPS) stimulation and (2) oxygen-glucose deprivation (OGD), versus combined LPS/OGD...
March 9, 2018: BMC Neuroscience
Karl-Ludwig Bruchhage, Sabrina Heinrichs, Barbara Wollenberg, Ralph Pries
It has been shown that head and neck squamous cell carcinoma (HNSCC) are infiltrated by plasmacytoid dendritic cells (pDCs). The HNSCC TH2 biased microenvironment leads to strong alterations of the cellular functions of pDC and thus impairs the initiation and function of adequate immune responses. In this work we comprehensively analyzed the capacity of CpG-oligonucleotides to activate interferon (IFN)-α secretion of human pDC in the presence of HNSCC. IFN-α secretion was measured using the ELISA Technique...
March 2018: Oncology Letters
Dan Zhou, Yun Zhu, Min-Zhi Ouyang, Ming Zhang, Kui Tang, Cheng-Cheng Niu, Ling Li
Toll-like receptor 4 (TLR4) is a transmembrane pattern‑recognition receptor expressed in immune cells and the heart. Activation of TLR4 signaling during sepsis results in the release of cardiac depression mediators that may impair heart function. The present study aimed to determine whether TLR4 contributes to development of severe sepsis‑induced myocardial dysfunction. A cecum ligation and puncture (CLP) procedure was employed to establish severe sepsis models. Wild type (WT) and TLR4 knock‑out (TLR4‑KO) mice were divided into four groups: WT‑sham, TLR4‑KO‑sham, WT‑CLP, and TLR4‑KO‑CLP...
January 25, 2018: Molecular Medicine Reports
Elżbieta Gałecka, Monika Talarowska, Michael Maes, Kuan-Pin Su, Paweł Górski, Anna Kumor-Kisielewska, Janusz Szemraj
BACKGROUND: Thyroid hormones (TH) are involved in modulation of the immune system and inflammation. TH dysregulation is associated with depressive disorders. The iodothyronine deiodinases (DIOs), the key enzymes for TH synthesis, can be affected and induced by pro-inflammatory cytokines. We aimed to investigate the levels of and correlation between type 2 DIO (DIO2) and interferon-gamma (IFN-ɣ) in patients with recurrent depressive disorders (rDD). METHODS: Data from 91 rDD patients and 105 healthy controls were analyzed...
January 20, 2018: Pharmacological Reports: PR
Zequan Zhang, Youtao Xie, Houhua Pan, Liping Huang, Xuebin Zheng
Biomaterial surface topography plays a vital role in the osteointegration of implants by regulating the early cell responses and tissue growth-in. However, most of the previous researches focused on the effects of osteogenic cells, only a little is known about the immune cells which dominate osteogenesis after implanting. In this paper, patterned titanium coatings were fabricated and the effects of surface topography on the macrophage behaviors were investigated. On patterned titanium surface, macrophages preferred to polarize to M2, while macrophages on traditional titanium coatings presented higher M1 polarization...
January 1, 2017: Journal of Biomaterials Applications
Siddhartha Mahanty, Miguel A Orrego, Carla Cangalaya, M Paz Adrianzen, Gianfranco Arroyo, Juan Calcina, Armando E Gonzalez, Héctor H García, Cristina Guerra-Giraldez, Theodore E Nash
BACKGROUND: Neurocysticercosis (NCC) is an infection of the brain with the larval cyst of the tapeworm, Taenia solium. Cysticidal treatment induces parasite killing resulting in a post inflammatory response and seizures, which generally requires corticosteroid treatment to control inflammation. The nature of this response and how to best control it is unclear. We investigated the anti-inflammatory effects of pretreatment with etanercept (ETN), an anti-tumor necrosis factor agent, or dexamethasone (DEX), a high potency corticosteroid, on the post treatment inflammatory response in naturally infected pigs with neurocysticercosis after a single dose of the cysticidal drug praziquantel (PZQ)...
November 2017: PLoS Neglected Tropical Diseases
Yazdan Azimi Fashi, Azadeh Mesripour, Valiollah Hajhashemi
OBJECTIVE: Interferon-α (IFN) therapy can cause depressive symptom which may lead to drug discontinuation. By interfering with tryptophan pathway, the available level of tryptophan required for serotonin synthesis decreases which could be related to depression. The aim of this study was to evaluate whether soybean diet could improve IFN-induced depression. MATERIALS AND METHODS: Male mice weighing 28±3 g were used in the forced swimming test (FST) as an animal model of depression; also, locomotor activity was recorded...
September 2017: Avicenna Journal of Phytomedicine
Alessandra Borsini, Annamaria Cattaneo, Chiara Malpighi, Sandrine Thuret, Neil A Harrison, Patricia A Zunszain, Carmine M Pariante
Background: In humans, interferon-α treatment for chronic viral hepatitis is a well-recognized clinical model for inflammation-induced depression, but the molecular mechanisms underlying these effects are not clear. Following peripheral administration in rodents, interferon-α induces signal transducer and activator of transcription-1 (STAT1) within the hippocampus and disrupts hippocampal neurogenesis. Methods: We used the human hippocampal progenitor cell line HPC0A07/03C to evaluate the effects of 2 concentrations of interferon-α, similar to those observed in human serum during its therapeutic use (500 pg/mL and 5000 pg/mL), on neurogenesis and apoptosis...
October 10, 2017: International Journal of Neuropsychopharmacology
C M Cooper, B Godlewska, A L Sharpley, E Barnes, P J Cowen, C J Harmer
BACKGROUND: Treatment of medical patients with the inflammatory cytokine, interferon-α (IFN-α), is frequently associated with the development of clinical depressive symptomatology. Several important biological correlates of the effect of IFN-α on mood have been described, but the neuropsychological changes associated with IFN-α treatment are largely unexplored. The aim of the present preliminary study was to assess the effect of IFN-α on measures of emotional processing. METHOD: We measured changes in emotional processing over 6-8 weeks in 17 patients receiving IFN-α as part of their treatment for hepatitis C virus infection...
September 11, 2017: Psychological Medicine
Andrea Alice Silva, Rafael Rodrigues Silva, Daniel Gibaldi, Rafael Meyer Mariante, Jessica Brandão Dos Santos, Isabela Resende Pereira, Otacílio Cruz Moreira, Joseli Lannes-Vieira
BACKGROUND: In conditions of immunosuppression, the central nervous sty 5ystem (CNS) is the main target tissue for the reactivation of infection by Trypanosoma cruzi, the causative agent of Chagas disease. In experimental T. cruzi infection, interferon gamma (IFNγ)(+) microglial cells surround astrocytes harboring amastigote parasites. In vitro, IFNγ fuels astrocyte infection by T. cruzi, and IFNγ-stimulated infected astrocytes are implicated as potential sources of tumor necrosis factor (TNF)...
September 6, 2017: Journal of Neuroinflammation
Charlotte K Callaghan, Jennifer Rouine, Reginald L Dean, Brian I Knapp, Jean M Bidlack, Daniel R Deaver, Shane M O'Mara
Patients receiving the cytokine immunotherapy, interferon-alpha (IFN-α) frequently present with neuropsychiatric consequences and cognitive impairments. Patients (25-80%) report symptoms of depression, including, anhedonia, irritability, fatigue and impaired motivation. Our lab has previously demonstrated treatment (170,000IU/kg sc, 3 times per week for 4weeks) of the pro-inflammatory cytokine, IFN-α, induced a depressive phenotype in rats in the forced swim test (FST). Here, we examine the biological mechanisms underlying behavioral changes induced by IFN-α, which may be reflective of mechanisms underlying inflammation associated depression...
January 2018: Brain, Behavior, and Immunity
Alexandria Hicks-Nelson, Gillian Beamer, Kursat Gurel, Rachel Cooper, Benjamin C Nephew
Similar to the multi-hit theory of schizophrenia, social behavior pathologies are mediated by multiple factors across generations, likely acting additively, synergistically, or antagonistically. Exposure to social adversity, especially during early life, has been proposed to induce depression symptoms through immune mediated mechanisms. Basal immune factors are altered in a variety of neurobehavioral models. In the current study, we assessed two aspects of a transgenerational chronic social stress (CSS) rat model and its effects on the immune system...
July 21, 2017: Brain Sciences
Charlotte K Callaghan, Jennifer Rouine, Shane M O'Mara
Aerobic exercise has marked effects on mood and cognition. Here, we used an interferon-alpha (IFN-α) induced depression model to evaluate the potential efficacy of chronic treadmill running on mood and cognition in the rat. IFN-α treatment induces behavioral deficits in the forced swim test (FST), open field test and object exploration task. Male han Wistar rats (n=8 per group, 3month old) were injected 3 times weekly with recombinant human IFN-α or saline (control) for 4weeks. One group was exercised 3 times (1h treadmill running) per week while the other remained sedentary...
July 12, 2017: Physiology & Behavior
Ayse Basak Engin, Atilla Engin
Obesity activates both innate and adaptive immune responses in adipose tissue. Elevated levels of eosinophils with depression of monocyte and neutrophil indicate the deficiencies in the immune system of morbidly obese individuals. Actually, adipose tissue macrophages are functional antigen-presenting cells that promote the proliferation of interferon-gamma (IFN-gamma)-producing CD4+ T cells in adipose tissue of obese subjects. Eventually, diet-induced obesity is associated with the loss of tissue homeostasis and development of type 1 inflammatory responses in visceral adipose tissue...
2017: Advances in Experimental Medicine and Biology
Charllyany Sabino Custódio, Bruna Stefânia Ferreira Mello, Adriano José Maia Chaves Filho, Camila Nayane de Carvalho Lima, Rafaela Carneiro Cordeiro, Fábio Miyajima, Gislaine Z Réus, Silvânia Maria Mendes Vasconcelos, Tatiana Barichello, João Quevedo, Antônio Carlos de Oliveira, David Freitas de Lucena, Danielle S Macedo
Early-life challenges, particularly infections and stress, are related to neuropsychiatric disorders such as autism and schizophrenia. Here, we conducted a wide range of behavioral tests in periadolescent (postnatal day (PN) 35) and adult (PN70) Swiss mice neonatally challenged with LPS on PN5 and -7, to unveil behavioral alterations triggered by LPS exposure. Immune and neurotrophic (brain-derived neurotrophic factor-BDNF) alterations were determined in the prefrontal cortex (PFC), hippocampus (HC), and hypothalamus (HT)...
May 23, 2017: Molecular Neurobiology
Anne Skøttrup Mørkholt, Ove Wiborg, Jette G K Nieland, Søren Nielsen, John Dirk Nieland
Major depressive disorder is a complex and common mental disease, for which the pathology has not been elucidated. The purpose of this study is to provide knowledge about the importance of mitochondrial dysfunction, dysregulated lipid metabolism and inflammation. Mitochondrial carnitine palmitoyl transferase 1a (CPT1a) is a key molecule involved in lipid metabolism and mutations in CPT1a causing reduced function is hypothesized to have a protective role in the development of depression. Moreover, CPT1a is found to be upregulated in suicide patients with history of depression...
May 19, 2017: Scientific Reports
Pei Wu, Yang Liu, Wei-Dan Jiang, Jun Jiang, Yong-An Zhang, Xiao-Qiu Zhou, Lin Feng
This study aimed to investigate the effects of choline deficiency on intestinal inflammation of fish after Aeromonas hydrophila infection and the potential molecular mechanisms. Juvenile Jian carp (Cyprinus carpio var. Jian) were fed two diets containing choline at 165 (deficient group) and 607 mg/kg diet respectively for 65 days. Choline deficiency decreased intestinal lysozyme activity, C3 and IgM contents, increased acid phosphatase activity, downregulated mRNA levels of antimicrobial peptides [liver-expressed antimicrobial peptide (LEAP) 2A, LEAP-2B, hepcidin and defensin], cytokines [interleukin (IL) 6a, tumor necrosis factor α (TNF-α), interferon γ2b (IFN-γ2b), IL-6b and transforming growth factor β2 (TGF-β2) only in proximal intestine, IL-10 in mid and distal intestine], immune-related signaling molecules [Toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), nuclear factor kappa B (NF-κB), inhibitor of NF-κB (IκB), Janus kinase 3 (JAK3), and signal transducers and activators of transcription 5 (STAT5)], tight junction proteins (claudin 3b, claudin 3c, claudin 11 and occludin), and mitogen-activated protein kinases p38 (p38MAPK ) in proximal and distal intestine of juvenile Jian carp after A...
June 2017: Fish & Shellfish Immunology
Andreas Baranyi, Omid Amouzadeh-Ghadikolai, Dirk von Lewinski, Robert J Breitenecker, Tatjana Stojakovic, Winfried März, Christoph Robier, Hans-Bernd Rothenhäusler, Harald Mangge, Andreas Meinitzer
Quinolinic acid, a macrophage/microglia-derived excitotoxin fulfills a plethora of functions such as neurotoxin, gliotoxin, and proinflammatory mediator, and it alters the integrity and cohesion of the blood-brain barrier in several pathophysiological states. Beta-trace protein (BTP), a monomeric glycoprotein, is known to indicate cerebrospinal fluid leakage. Thus, the prior aim of this study was to investigate whether BTP might non-invasively indicate quinolinic acid-induced impaired blood-brain barrier integrity...
March 9, 2017: Scientific Reports
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