Effects of fluoxetine and venlafaxine in the mouse neural embryonic stem cell test
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE153836 | GEO | 2021/02/27
REPOSITORIES: GEO
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Project description:Effects of fluoxetine and venlafaxine in the mouse neural embryonic stem cell test
| PRJNA644338 | ENA
Project description:This study investigates the effects of environmentally-relevant concentrations of fluoxetine (FLX, commercial name: Prozac) on wound healing. Pollution of water systems with pharmaceutical and care products, including antidepressants such as FLX and other selective serotonin reuptake inhibitors, is a growing environmental concern. Environmentally-relevant FLX concentrations are known to impact physiological functions and behaviour of aquatic animals, however, the effects of exposure on humans are currently unknown. Using a combination of human skin biopsies and keratinocyte cell lines, we show that exposure to environmental FLX enhances wound closure. We show dose-dependent increases in wound closure with FLX concentrations from 125 ng/l. We demonstrate that the mechanisms underlying enhanced wound closure are increased cell proliferation and serotonin signalling. Transcriptomic analysis revealed 350 differentially expressed genes after exposure. Downregulated genes were enriched in pathways related to mitochondrial function and metabolism, while upregulated genes were associated with cell proliferation and tissue morphogenesis. Kinase profiling showed altered phosphorylation of kinases related to the MAPK pathway. Consistent with this, phosphoproteomics analyses identified 235 differentially phosphorylated proteins after exposure, with enriched GO terms related to cell cycle, division, and protein biosynthesis. These findings collectively show that exposure to environmental FLX promotes wound healing through modulation of serotonin signalling, gene expression and protein phosphorylation, leading to enhanced cell proliferation. Our results open the door for further research to investigate the effects of environmental FLX on cell metabolism and proliferation, and clinical applications of FLX in the setting of wound healing. We argue that there is an urgent need to develop models that can inform on the risks, and potential benefits, of environmental pollution with selective serotonin reuptake inhibitors.
2024-09-13 | GSE268987 | GEO
Project description:Chronic social isolation (CSIS) is a risk factor for human major depressive disorder (MDD). Fluoxetine (Flx) is an antidepressant commonly used for first-line MDD therapy. However, its downstream mechanisms of action, beyond serotonergic signaling, remain elusive. We aimed to analyze the effects of CSIS followed by chronic Flx treatment on proteome changes in the adult male rat prefrontal cortex (PFC) cytosolic and non-synaptic mitochondria (NSM)-enriched fractions. Treatment with Flx ameliorated depression-like behaviors in CSIS-induced rat model of depression as assessed by sucrose preference test and forced swim test. Proteomic data showed that Flx increased the expression of proteins involved in cytoskeleton and regulation of intracellular Ca2+ homeostasis in the cytosol and of enzymes linking the glycolytic pathway to the citric acid cycle (Dlat) and ATPase-coupled ion transmembrane transport in NSM. CSIS resulted in down-regulation of cytosolic proteins involved in proteasome/ubiquitination processes and glutathione antioxidative system and up-regulated expression of key enzymes participating in oxidative phosphorylation. Presence of cytochrome c in the cytosol indicated compromised mitochondrial membrane integrity. Flx treatment in CSIS rats showed predominately an upregulation of vesicle-mediated transport proteins and reduced Uqcrfs1 along with transport in NSM, favoring reduced energy metabolism. Our data suggest that proteins from both cytosol and NSM-enriched fractions are affected by Flx in a key brain region associated with stress response, cognitive process and regulation of emotion.
2023-11-10 | PXD026202 | Pride
Project description:Major depressive disorder (MDD) is the psychiatric disorder with the highest prevalence in the world. Pharmacological antidepressant treatment (AD), such as selective serotonin reuptake inhibitors [SSRI, i.e. fluoxetine (Flx)] is the first line of treatment for MDD. Despite its efficacy, lack of AD response occurs in numerous patients characterizing Difficult-to-treat Depression. ElectroConvulsive Therapy (ECT) is a highly effective treatment inducing rapid improvement in depressive symptoms and high remission rates of ~50–63% in patients with pharmaco-resistant depression. Nevertheless, the need to develop reliable treatment response predictors to guide personalized AD strategies and supplement clinical observation is becoming a pressing clinical objective. Here, we propose to establish a proteomic peripheral biomarkers signature of ECT response in an anxio/depressive animal model of non-response to AD. Using an emotionality score based on the analysis complementary behavioral tests of anxiety/depression (Elevated Plus Maze, Novelty Suppressed Feeding, Splash Test), we showed that a 4-week corticosterone treatment (35 μg/ml, Cort model) in C57BL/6JRj male mice induced an anxiety/depressive-like behavior. A 28-days chronic fluoxetine treatment (Flx, 18 mg/kg/day) reduced corticosterone-induced increase in emotional behavior. A 50% decrease in emotionality score threshold before and after Flx, was used to separate Flx-responding mice (Flx-R, n=18), or Flx non-responder mice (Flx-NR, n=7). Then, Flx-NR mice received 7 sessions of electroconvulsive seizure (ECS, equivalent to ECT in humans) and blood was collected before and after ECS treatment. Chronic ECS normalized the elevated emotionality observed in Flx-NR mice. Then, proteins were extracted from peripheral blood mononuclear cells (PBMCs) and isolated for proteomic analysis using a high-resolution MS Orbitrap. The proteomic analysis revealed a signature of 33 peripheral proteins associated with response to ECS (7 down- and 26 upregulated). These proteins were previously associated with mental disorders and involved in regulating pathways which participate to the depressive disorder etiology. remark for sample name : ECTR=Flx-NR-ES, C=cort/Veh, CFNR= Flx-NR
2022-11-01 | PXD037392 | Pride
Project description:It is well-known that between 40 and 50% of patients taking antidepressants do not respond to treatment or relapse. Genome wide gene expression studies can help us to understand better the response to antidepressants, revealing the effects of both genetic background and environmental/epigenetic factors. We used microarrays to detail the response to Fluoxetine in children and adolescents, analysing the expression just before intake of drug and 8 weeks after starting the treatment.
2019-12-31 | GSE128387 | GEO
Project description:Groups of 8 adult BALB/c male mice were either untreated or exposed for 9 weeks to unpredicatble chronic mild stress (UCMS), or exposed for 7 weeks to UCMS and treated for the last 5 weeks with fluoxetine (Flx) diluted in drinking water, or untreated for 2 weeks and received Flx for 5 weeks. Total RNAs from whole blood (WB) were profiled after hybridization with Agilent SurePrint G3 Mouse GE 8x60K Microarray v1 to identify transcriptional biomarkers of major depression.
2017-09-14 | GSE84184 | GEO
Project description:Our previous study suggested persistent transgenerational effects of fluoxetine (FLX) exposure, in both environmental and therapeutic concentrations, on stress response and behaviour up to 3 generation withdrawn from exposure in larvae and adult zebrafish. To lay the foundations of the mechanistic of such transgenerational effects, we studied the effect of FLX on stress response in brain tissues (telencephalon and hypothalamus) of larvae and adult zebrafish using differentially expressed genes at the transcriptome level. To monitor the stress response, we used a transgenic zebrafish line (SR4G) which are expressing green fluorescence protein (GFP) in response to endogenous and exogenous glucocorticoids. The transcriptome analysis of GFP RNA as an internal control, provided us with an invaluable tool to clearly visualize and differentiate between stressed and unstressed groups as per treatments. To stimulate stress in both larvae and adult zebrafish we used a modified net stressing technique consisting of consecutive sequence of air exposure and incubation intervals. A pool of 22 larvae heads and a pool of 5 telencephalon and 5 hypothalamus dissected tissues were used as the target tissues for RNA extraction. All experiments were replicated in n=6 per 4 different groups including Control-Unstressed (Cnt-U), Control-Stressed (Cnt-S), Fluoxetine-Unstressed (FLX-U), and Fluoxetine-Stressed (FLX-S) using pools of larvae heads, telencephalon, and hypothalamus. After total RNA extraction, using Illumina technology all samples were sequence and the list of differentially expressed genes (DEGs) were produced using DSEQ pipeline in R.
2022-04-26 | GSE141144 | GEO
Project description:Groups of 8 adult BALB/c male mice were either untreated or exposed for 9 weeks to unpredicatble chronic mild stress (UCMS), or exposed for 7 weeks to UCMS and treated for the last 5 weeks with fluoxetine (Flx) diluted in drinking water, or untreated for 2 weeks and received Flx for 5 weeks. Total RNAs from dentate gyrus (DG) and anterior cingulate cortex (ACC) were profiled after hybridization with Agilent SurePrint G3 Mouse GE 8x60K Microarray v1 to identify transcriptional biomarkers of major depression.
2017-09-14 | GSE84183 | GEO
Project description:Contamination of aquatic ecosystems with anthropogenic pollutants, including pharmaceutical drugs, is a major concern worldwide. Fish are particularly at risk of exposure to pollutants but their impacts on mineralized fish tissues, particularly the scales that form a barrier between the fish and the environment, are poorly understood. The proteome data here presented support the findings reported in the associated research article “Disruption of the sea bass (Dicentrarchus labrax) skin-scale by estradiol and fluoxetine, an emerging pollutant”. Juvenile sea basses were exposed by intraperitoneal injections to: a) the antidepressant fluoxetine (FLX), a widely prescribed psychotropic drug and an emerging pollutant; b) the natural estrogen 17β-estradiol (E2) and c) coconut oil alone (control). The scale proteome profiles of fish exposed to these compounds for 5 days were analysed by the quantitative label-free proteomics technology SWATH-MS (Sequential Windowed data-independent Acquisition of the Total High-resolution-Mass Spectra). LC-MS data from pooled protein extracts from the scales of all experimental groups were acquired using information-dependent acquisition (IDA), which allowed the identification of 1,254 proteins through searches against the sea bass genome database. 715 proteins were confidently quantified by SWATH acquisition, from which 213 proteins had modified levels (p<0.05) between E2- or FLX-exposed fish and control. The main biological processes and KEGG pathways affected by E2 or FLX treatments were identified using Cytoscape/ClueGO enrichment analyses.
2022-01-11 | PXD020983 | Pride
Project description:Identifying adequate biomarkers of major depressive disorder (MDD) and therapy has been the goal of many studies. Many molecular alterations associated with the pathophysiology of MDD reside within the synapse. Fluoxetine (Flx) is the most commonly prescribed antidepressant, but the mechanism of its action is unclear. Hence, we performed a comparative proteomics of synaptosomal-enriched fractions from prefrontal cortex of adult male Wistar rats exposed to CSIS (6 weeks) and after chronic Flx treatment of controls (3 weeks) and CSIS-exposed rats (lasting 3 weeks of 6-week-CSIS). Our aim was to profile synaptosomal proteome changes representative of possible time-consuming events underlying the CSIS-induced depressive-like behavior and antidepressant property of Flx. Bioinformatic data of Flx-treated control rats revealed down-expression of proteins that mainly participate in proteasome system and vesicle mediated transport as well as predominantly increases expression of exocytosis-associated proteins. CSIS led to decreased expression of proteins involved in ATP metabolic process, synaptic vesicle endocytosis and proteasome system, while increased energy yielding glycolytic pathway. Flx treatment of CSIS rats predominantly increases expression of exo/endocytosis-associated proteins and Cox5a, mitochondria-associated proteins involved in oxidative phosphorylation. Overall, synaptoproteomic profiling indicated that Flx stimulated synaptic vesicular dynamics by enhancing endo/exocytosis and mitochondrial energy metabolism in CSIS rats that might be critical targets for pharmacological treatments for MDD.
2023-11-10 | PXD029575 | Pride