Transcription profiling of dentate gyrus and anterior cingulate cortex in mice exposed Unpredicatble Chronic Mild Stress and treated with fluoxetine
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE84183 | GEO | 2017/09/14
SECONDARY ACCESSION(S): PRJNA328247
REPOSITORIES: GEO
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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: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
Project description:Major depression is a multidimensional disorder highly prevalent in modern society. Although several classes of antidepressants (ADs) are currently available to treat depression, the effectiveness of treatment is still limited, as many patients do not show full remission; thus, there is a need to find better patients’ directed therapeutic strategies. Neuroplastic changes in several brain regions, namely in the hippocampal dentate gyrus (DG), are amongst the best correlates of depression and of ADs actions. In this study the targets and molecular mediators of chronic stress and of four ADs from different pharmacological classes (fluoxetine, imipramine, tianeptine and agomelatine) were investigated in the DG. Using the unpredictable chronic mild stress (uCMS) animal model of depression, the molecular commonalities and specificities of the ADs were determined. All ADs, except agomelatine, could reverse the behavioral deficits produced by uCMS, and the neuroplastic changes in the DG; agomelatine reversed only the anhedonic profile in the sucrose consumption test. Chronic stress induced mild but relevant molecular changes that were mostly reversed by fluoxetine, imipramine and tianeptine. Fluoxetine reduced pro-inflammatory response and increased cell metabolism pathways. Its actions were mostly dependent on molecular changes occurring in neurons. Similarities were found between imipramine and tianeptine molecular actions and targets, as both activated pathways related to cellular protection. Moreover, no particular neural cell type enrichment was found with both treatments. Agomelatine presented a very dissimilar molecular pattern impacting greatly on Rho-GTPases-related pathways in oligodendrocytes and neurons. The recognition of these molecular alterations contributes to the understanding of the processes implicated in the onset and treatment of depression and may pave the way for more effective therapeutic interventions. We compared gene expresssion in the dentate gyros of rats which were either untreated, exposed to unpredictable chronic mild stress, or exposed to the same stress and treated with either fluoxetine, imipramine, tianeptine, or agomelatine
2015-07-02 | E-GEOD-56028 | biostudies-arrayexpress
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:The gene expression patterns in the dentate gyrus of wild-type mice treated with fluoxetine (15 mg/kg/day for 3 weeks) or vehicle were examined using Affymetrix GeneChip arrays.
2019-02-25 | GSE118669 | GEO
Project description:Transcription profiling of blood, dentate gyrus and anterior cingulate cortex in mice exposed Unpredicatble Chronic Mild Stress and treated with fluoxetine
| PRJNA328242 | ENA
Project description:Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine are the most common treatment for major depression. However, approximately 50% of depressed patients fail to achieve an effective treatment response. Understanding how gene expression systems relate to treatment responses may be critical for understanding antidepressant resistance. Transcriptome profiling allows for the simultaneous measurement of expression levels for thousands of genes and the opportunity to utilize this information to determine mechanisms underlying antidepressant treatment responses. However, the best way to relate this immense amount of information to treatment resistance remains unclear. We take a novel approach to this question by examining dentate gyrus transcriptomes from the perspective of a stereotyped fluoxetine-induced gene expression program. Expression programs usually represent stereotyped changes in expression levels that occur as cells transition phenotypes. Fluoxetine will shift transcriptomes so they lie somewhere between a baseline state and a full-response at the end of the program. The position along this fluoxetine-induced gene expression program (program status) was measured using principal components analysis (PCA). The same expression program was initiated in treatment-responsive and resistant mice but treatment response was associated with further progression along the fluoxetine-induced gene expression program. The study of treatment-related differences in gene expression program status represents a novel way to conceptualize differences in treatment responses at a transcriptome level. Understanding how antidepressant-induced gene expression program progression is modulated represents an important area for future research and could guide efforts to develop novel augmentation strategies for antidepressant treatment resistant individuals. 38 samples, 2 dentate regions (dorsal/ventral), 3 groups (control, antidepressant resistant (4 mice), antidepressant responsive (7 mice), untreated (8 mice).
2013-12-31 | E-GEOD-43261 | biostudies-arrayexpress
Project description:Fluoxetine (FLX) is the most common selective serotonin reuptake inhibitor pharmaceutical used for the treatment of psychological disorders such as depression and anxiety. Increased prescription use of FLX by human populations has led to its pseudo-persistence in effluent-receiving waterways. Despite emerging concerns of FLX becoming a potential threat to the aquatic environment, there is currently limited information on effects of FLX on aquatic wildlife, including its specific mechanism of action and associated toxicity pathways in fish. The main goal of this study was to identify and validate key molecular toxicity pathways that are predictive of apical endpoints induced by exposure to FLX using the fathead minnow (Pimephales promelas), a model species common to North American freshwater systems. Adult fathead minnows were exposed to three concentrations of FLX (2.42, 10.7, and 56.7 µg/L) and a control for 21 days. After 96 hours, a subset of fish was sampled, and liver and brain tissue were collected to characterize molecular toxicity pathways using whole transcriptome and proteome analyses. In addition, at the end of the 21-day exposure, individuals were assessed for apical outcomes of regulatory relevance including histopathology and fecundity. Differential gene expression observed in the liver of fish exposed to the highest FLX treatment and revealed dysregulation of pathways associated with biosynthesis and metabolism of fatty acids, which may be an upstream molecular response that led to lipid-type vacuolation of hepatocytes, as observed in the histology analysis. Whole proteome analysis of the same fish revealed dysregulation of PPAR signalling, which may be associated with the enrichment of lipid-related pathways observed in the transcriptome. In addition, there was an indication of pathway enrichment of transcription- and translation-related pathways in the proteome. Common dysregulated genes in the brain of the treated fish were related to cellular signalling processes that are influenced by serotonin levels and shown to be involved in reproductive behaviour and, in turn, reproductive success. This was confirmed through a significant decrease in fecundity following the 21-day exposure. Pathways to measurable adverse outcomes are complex, however, this research does provide some important clues to the mechanistic toxicity that FLX inflicts.
2022-02-27 | GSE182913 | GEO
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:We used comparative proteomic approach to identify proteome changes in purified synaptic terminals (synaptosomes) of rats exposed to chronic social isolation (CSIS) (6 weeks), animal model for depression, followed by chronic Fluoxetine treatment (last 3 weeks of CSIS) (therapeutic effect). Our aim was to examine a subcellular compartment enriched in proteins involved in synaptic function.
2023-03-11 | PXD028816 | Pride