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antidepressant and proteomics

Uhna Sung, Francesca Binda, Valentina Savchenko, William A Owens, Lynette C Daws
The antidepressant-sensitive norepinephrine (NE) transporter (NET) inactivates NE released during central and peripheral neuronal activity by transport into presynaptic cells. Altered NE clearance due to dysfunction of NET has been associated with the development of mental illness and cardiovascular diseases. NET activity in vivo is influenced by stress, neuronal activity, hormones and drugs. We investigated the mechanisms of Ca(2+) regulation of NET and found that Ca(2+) influenced both Vmax and Km for NE transport into cortical synaptosomes...
December 23, 2016: Journal of Chemical Neuroanatomy
Dong Ik Park, Carine Dournes, Inge Sillaber, Manfred Uhr, John M Asara, Nils C Gassen, Theo Rein, Marcus Ising, Christian Webhofer, Michaela D Filiou, Marianne B Müller, Christoph W Turck
Selective Serotonin Reuptake Inhibitors (SSRIs) are commonly used drugs for the treatment of psychiatric diseases including major depressive disorder (MDD). For unknown reasons a substantial number of patients do not show any improvement during or after SSRI treatment. We treated DBA/2J mice for 28 days with paroxetine and assessed their behavioral response with the forced swim test (FST). Paroxetine-treated long-time floating (PLF) and paroxetine-treated short-time floating (PSF) groups were stratified as proxies for drug non-responder and responder mice, respectively...
October 12, 2016: Scientific Reports
Lucia Carboni, Thanh-Phuong Nguyen, Laura Caberlotto
PURPOSE: The pathophysiological basis of major depression is incompletely understood. Recently, numerous proteomic studies have been performed in rodent models of depression to investigate the molecular underpinnings of depressive-like behaviours with an unbiased approach. The objective of the study is to integrate the results of these proteomic studies in depression models to shed light on the most relevant molecular pathways involved in the disease. EXPERIMENTAL DESIGN: Network analysis is performed integrating preexisting proteomic data from rodent models of depression...
December 2016: Proteomics. Clinical Applications
Yongtao Yang, Jin Chen, Chengyu Liu, Liang Fang, Zhao Liu, Jing Guo, Ke Cheng, Chanjuan Zhou, Yuan Zhan, Narayan D Melgiri, Liang Zhang, Jiaju Zhong, Jianjun Chen, Chenglong Rao, Peng Xie
Although an association between major depressive disorder (MDD) and suicide exists, most depressed patients never attempt suicide. An improved understanding of the factors contributing to suicidal risk in MDD can provide direction for suicide predictor development. In MDD suicide attempters (MDD-SA), MDD non-attempters (MDD-NA), and healthy controls (HC) (n = 12 each group), complementary plasma proteomics identified 45 differential proteins mapped to coagulation and inflammation, 25 of which underwent Western blotting...
2016: Scientific Reports
Helena Kaihola, Fatma G Yaldir, Julius Hreinsson, Katarina Hörnaeus, Jonas Bergquist, Jocelien D A Olivier, Helena Åkerud, Inger Sundström-Poromaa
The use of antidepressant treatment during pregnancy is increasing, and selective serotonin reuptake inhibitors (SSRIs) are the most widely prescribed antidepressants in pregnant women. Serotonin plays a role in embryogenesis, and serotonin transporters are expressed in two-cell mouse embryos. Thus, the aim of the present study was to evaluate whether fluoxetine, one of the most prescribed SSRI antidepressant world-wide, exposure influences the timing of different embryo developmental stages, and furthermore, to analyze what protein, and protein networks, are affected by fluoxetine in the early embryo development...
2016: Frontiers in Cellular Neuroscience
Barbara Gellén, Katalin Völgyi, Balázs András Györffy, Boróka Balogh, Zsuzsa Darula, Éva Hunyadi-Gulyás, Péter Baracskay, András Czurkó, István Hernádi, Gábor Juhász, Árpád Dobolyi, Katalin Adrienna Kékesi
: Neonatal rodents chronically treated with the tricyclic antidepressant clomipramine show depression-like behavior, which persists throughout adulthood. Therefore, this animal model is suitable to investigate the pathomechanism of depression, which is still largely unknown at the molecular level beyond monoaminergic dysfunctions. Here, we describe protein level changes in the prefrontal cortex of neonatally clomipramine-treated adult rats correlating with behavioral abnormalities. Clomipramine was administered to rat pups twice daily between postnatal days 8-21, while controls received saline injections...
June 29, 2016: Journal of Proteomics
Raymond W Lam, Roumen Milev, Susan Rotzinger, Ana C Andreazza, Pierre Blier, Colleen Brenner, Zafiris J Daskalakis, Moyez Dharsee, Jonathan Downar, Kenneth R Evans, Faranak Farzan, Jane A Foster, Benicio N Frey, Joseph Geraci, Peter Giacobbe, Harriet E Feilotter, Geoffrey B Hall, Kate L Harkness, Stefanie Hassel, Zahinoor Ismail, Francesco Leri, Mario Liotti, Glenda M MacQueen, Mary Pat McAndrews, Luciano Minuzzi, Daniel J Müller, Sagar V Parikh, Franca M Placenza, Lena C Quilty, Arun V Ravindran, Tim V Salomons, Claudio N Soares, Stephen C Strother, Gustavo Turecki, Anthony L Vaccarino, Fidel Vila-Rodriguez, Sidney H Kennedy
BACKGROUND: Major Depressive Disorder (MDD) is among the most prevalent and disabling medical conditions worldwide. Identification of clinical and biological markers ("biomarkers") of treatment response could personalize clinical decisions and lead to better outcomes. This paper describes the aims, design, and methods of a discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). The CAN-BIND research program investigates and identifies biomarkers that help to predict outcomes in patients with MDD treated with antidepressant medication...
April 16, 2016: BMC Psychiatry
M J Bebianno, S Sroda, T Gomes, P Chan, E Bonnafe, H Budzinski, F Geret
The increase use of pharmaceutical compounds in veterinary practice and human population results in the ubiquitous presence of these compounds in aquatic ecosystems. Because pharmaceuticals are highly bioactive, there is concern about their toxicological effects in aquatic organisms. Therefore, the aim of this study was to assess the effects of an effluent from a psychiatric hospital (containing a complex mixture of 25 pharmaceutical compounds from eleven therapeutic classes) on the freshwater clam Corbicula fluminea using a proteomic approach...
March 2016: Environmental Science and Pollution Research International
L Ruiz-Perera, M Muniz, G Vierci, N Bornia, L Baroncelli, A Sale, F M Rossi
The scarce functional recovery of the adult CNS following injuries or diseases is largely due to its reduced potential for plasticity, the ability to reorganize neural connections as a function of experience. Recently, some new strategies restoring high levels of plasticity in the adult brain have been identified, especially in the paradigmatic model of the visual system. A chronic treatment with the anti-depressant fluoxetine reinstates plasticity in the adult rat primary visual cortex, inducing recovery of vision in amblyopic animals...
2015: Scientific Reports
M Bot, M K Chan, R Jansen, F Lamers, N Vogelzangs, J Steiner, F M Leweke, M Rothermundt, J Cooper, S Bahn, B W J H Penninx
Much has still to be learned about the molecular mechanisms of depression. This study aims to gain insight into contributing mechanisms by identifying serum proteins related to major depressive disorder (MDD) in a large psychiatric cohort study. Our sample consisted of 1589 participants of the Netherlands Study of Depression and Anxiety, comprising 687 individuals with current MDD (cMDD), 482 individuals with remitted MDD (rMDD) and 420 controls. We studied the relationship between MDD status and the levels of 171 serum proteins detected on a multi-analyte profiling platform using adjusted linear regression models...
July 14, 2015: Translational Psychiatry
Mark J Niciu, Daniel C Mathews, Dawn F Ionescu, Erica M Richards, Maura L Furey, Peixiong Yuan, Allison C Nugent, Ioline D Henter, Rodrigo Machado-Vieira, Carlos A Zarate
BACKGROUND: Recently, surrogate neurobiological biomarkers that correlate with target engagement and therapeutic response have been developed and tested in early phase studies of mood disorders. OBJECTIVE: The identification of biomarkers could help develop personalized psychiatric treatments that may impact public health. METHODS: These biomarkers, which are associated with clinical response post-treatment, can be directly validated using multimodal approaches including genetic tools, proteomics/metabolomics, peripheral measures, neuroimaging, biostatistical predictors, and clinical predictors...
2014: Revista de Psiquiatria Clínica
Michael Maes, Gabriel Nowak, Javier R Caso, Juan Carlos Leza, Cai Song, Marta Kubera, Hans Klein, Piotr Galecki, Cristiano Noto, Enrico Glaab, Rudi Balling, Michael Berk
Meta-analyses confirm that depression is accompanied by signs of inflammation including increased levels of acute phase proteins, e.g., C-reactive protein, and pro-inflammatory cytokines, e.g., interleukin-6. Supporting the translational significance of this, a meta-analysis showed that anti-inflammatory drugs may have antidepressant effects. Here, we argue that inflammation and depression research needs to get onto a new track. Firstly, the choice of inflammatory biomarkers in depression research was often too selective and did not consider the broader pathways...
July 2016: Molecular Neurobiology
Lin Ge, Ming-Ming Zhu, Jing-Yu Yang, Fang Wang, Rong Zhang, Jing-Hai Zhang, Jing Shen, Hui-Fang Tian, Chun-Fu Wu
Depression is a complex psychiatric disorder, and its etiology and pathophysiology are not completely understood. Depression involves changes in many biogenic amine, neuropeptide, and oxidative systems, as well as alterations in neuroendocrine function and immune-inflammatory pathways. Oleamide is a fatty amide which exhibits pharmacological effects leading to hypnosis, sedation, and anti-anxiety effects. In the present study, the chronic mild stress (CMS) model was used to investigate the antidepressant-like activity of oleamide...
April 2015: Pharmacology, Biochemistry, and Behavior
Lucia Carboni
The neurobiological basis of major depressive disorder (MDD) is only partially understood. The proposed hypotheses postulate dysregulations of monoaminergic and other neurotransmitter pathways, impaired stress responses, insufficient neurogenetic and neurotrophic processes generating maladaptive neuroplasticity, inappropriate inflammatory and metabolic responses. Proteomic approaches can provide useful contributions to the investigation of the molecular neurobiology of MDD due to their open-ended nature. Studies performed in brain regions of MDD patients which had received antidepressant (AD) treatment showed that affected proteins mainly belonged to energy pathways, transport of molecules, signaling, and synaptic transmission...
October 2015: Proteomics. Clinical Applications
Sinead M O'Donovan, Shane O'Mara, Michael J Dunn, Declan M McLoughlin
Electroconvulsive therapy (ECT) is the most acutely effective treatment available for severe depression. However, its mechanism of action is not fully understood. Elucidating the protein changes induced in the brain by ECT will enhance our understanding of this antidepressant therapy. Electroconvulsive stimulation (ECS), the animal analogue of ECT, was administered to rats to determine the proteomic changes induced in the hippocampus, a region of the brain implicated in the biology of depression and its treatment...
December 17, 2014: Brain Research
Hendrik Wesseling, Hassan Rahmoune, Mark Tricklebank, Paul C Guest, Sabine Bahn
There is substantial interest in the N-methyl-d-aspartate (NMDA) receptor antagonist ketamine in psychiatric research because it exerts acute psychotomimetic and rapid antidepressant effects in rodents and humans. Here, we investigated proteomic changes in brain and serum after acute treatment of rats with ketamine using two targeted proteomic profiling methods. Multiplex immunoassay profiling of serum identified altered levels of interleukin 4, tumor necrosis factor alpha, and fibroblast growth factor 9, suggesting a link between ketamine exposure and peripheral inflammation and growth factor dysregulation...
January 2, 2015: Journal of Proteome Research
Daeyoung Oh, Mi Ran Choi, Dal Mu Ri Han, Young Gyu Chai, Joonho Choi
Fluoxetine, a serotonin-selective reuptake inhibitor, exerts antidepressant and antianxiety effects on major depressive and anxiety disorders. Previous studies suggest that treatment with fluoxetine influences the expression of various proteins that are involved in proliferation, differentiation, and apoptosis in the neuronal cells of the brain. However, many aspects of the molecular pathways that modulate antidepressant action are not well understood. Here, with the aim of identifying proteins involved in antidepressant action, we examined the protein expression profile of human embryonic carcinoma (NCCIT) cells in response to fluoxetine treatment using proteomic techniques such as two-dimensional gel electrophoresis and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS)...
December 3, 2014: Neuroreport
Antonino Glaviano, Sinead M O'Donovan, Karen Ryan, Shane O'Mara, Michael J Dunn, Declan M McLoughlin
Electroconvulsive therapy (ECT) is an effective antidepressant treatment, but its molecular mechanisms of action remain to be fully elucidated. To better understand the effects of ECT, we conducted a proteomic study to characterize global changes in plasma protein abundance induced by electroconvulsive stimulation (ECS) in the animal model equivalent of ECT. Male Sprague-Dawley rats were administered a single or repeat (10 sessions) course of ECS, and compared with sham-ECS administered animals. Quantitative differential protein expression analysis was performed, using 2-dimensional difference in gel electrophoresis (2D DiGE), on immunodepleted plasma...
December 2014: Journal of Psychopharmacology
Shih-Hang Lin, Wei-Cheng Chen, Kuan-Hung Lu, Pei-Ju Chen, Shu-Chen Hsieh, Tzu-Ming Pan, Shui-Tein Chen, Lee-Yan Sheen
Nowadays, depression is a serious psychological disorder that causes extreme economic loss and social problems. Previously, we discovered that the water extract of Gastrodia elata Blume (WGE) improved depressive-like behavior by influencing neurotransmitters in rats subjected to the forced swimming test. To elucidate possible mechanisms, in the present study, we performed a proteomics and bioinformatics analysis to identify the related pathways. Western blot-validated results indicated that the core protein network modulated by WGE administration was closely associated with down-regulation of the Slit-Robo pathway, which modulates neuronal cytoskeletal remodeling processes...
October 29, 2014: Journal of Agricultural and Food Chemistry
Viktoria Stelzhammer, Frieder Haenisch, Man K Chan, Jason D Cooper, Johann Steiner, Hannah Steeb, Daniel Martins-de-Souza, Hassan Rahmoune, Paul C Guest, Sabine Bahn
Major depressive disorder (MDD) is a complex and multi-factorial disorder. Although genetic factors and other molecular aspects of MDD have been widely studied, the underlying pathological mechanisms are still mostly unknown. We sought to investigate the pathophysiology of MDD by identifying and characterising serum molecular differences and their correlation to symptom severity in first onset, antidepressant drug-naïve MDD patients. We performed an exploratory molecular profiling study on serum samples of MDD patients and controls using multiplex immunoassay and label-free liquid chromatography mass spectrometry in data independent mode (LC-MSE)...
October 2014: International Journal of Neuropsychopharmacology
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