Shared and unique transcriptomic signatures of antidepressant and probiotics action in the mammalian brain
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE222756 | GEO | 2024/06/06
REPOSITORIES: GEO
Similar Datasets
Project description:To comprehensively characterize the intrinsic molecular effects of ADs independently of the specifics of particular disease models, we generated 300 transcriptomic profiles from 10 brain regions in naive rats. Three classical tricyclic antidepressants, Bupropion, desipramine, fluoxetine, and a probiotic formulation (Lacidofil®) can massively alter gene expression in most regions [>1,500 differentially expressed genes (DEGs)], suggesting that traditional single-gene or single-pathway analyses may under-represent the complexity of molecular responses. Using spatial transcriptomics in the prefrontal cortex from an independent set of animals, we further delineated DEGs and molecular pathways that exhibited layer-specific differential regulation by probiotics and fluoxetine.
2024-06-06 | GSE233571 | GEO
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:The identification of cell-type-specific and early-activated pharmacological targets of antidepressants might help to implement the search for alternative targets to develop drugs with safer side-effect profiles and faster onset of actions. Glia cells are active partners of neurons and blood vessels in supporting a variety of functions such as synaptic communication and blood-brain barrier permeability. Impaired glia cells (astrocytes and microglia cells) characterize postmortem brains of major depressive disorder patients, suggesting that they might be specifically modulated by pharmacological treatments to reverse disease phenotypes. Here, we have treated rat C6 glioma cells, used as a model of astrocytes, with two different classes of antidepressants (desipramine and fluoxetine) and two drugs without antidepressant properties (haloperidol and diazepam) to compare transcriptomes of glia cells after treatment with antidepressants versus drugs without antidepressant properties. To this aim, we used microarrays to detail the global early-activated cell-type-specific gene expression program and identified multiple classes of genes selectively modulated by antidepressants in astrocytes.
2016-11-16 | GSE89873 | GEO
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.
2015-07-02 | GSE56028 | GEO
Project description:Analysis of chronic treatment with a tricyclic antidepressant (desipramine) at gene expression level in hippocampus of mice bred for high (HA) or low (LA) swim stress-induced analgesia (SSIA).
2011-02-26 | GSE27532 | GEO
Project description:Analysis of chronic treatment with a tricyclic antidepressant (desipramine) at gene expression level in hippocampus of mice bred for high (HA) or low (LA) swim stress-induced analgesia (SSIA). Total RNA obtained from isolated hippocampi of HA and LA mice subjected to 21 intraperitoneal injections of desipramine hydrochloride (7.5 mg/kg/day) compared to total RNA obtained from isolated hippocampi of HA and LA mice subjected to 21 intraperitoneal injections of saline.
2011-02-26 | E-GEOD-27532 | biostudies-arrayexpress
Project description:Acid sphingomyelinase (ASM) inhibitors, which are clinically used as anti-depressants for ~60 years, have recently been shown to enhance stroke recovery in rodents. Using mice and cerebral microvascular endothelial cells exposed to ischemia/reperfusion (I/R) we show that the antidepressants amitriptyline, fluoxetine and desipramine induce angiogenesis in an ASM-dependent way by releasing small extracellular vesicles (sEVs) from endothelial cells, which have bona fide characteristics of exosomes and which, similar to sEVs released during I/R, promote angiogenesis. Post-I/R, ASM inhibition elicits a profound brain remodeling response with increased blood-brain barrier integrity, reduced brain leukocyte infiltrates and increased neuronal survival. The ASM inhibitor-mediated release of sEVs has disclosed an elegant target, via which stroke recovery can be amplified. Key words: Antidepressant, ceramide, exosome, focal cerebral ischemia, middle cerebral artery occlusion, sphingomyelin, stroke recovery
2022-10-14 | PXD024106 | Pride
Project description:Accumulating evidence demonstrates that the gut microbiota affects brain function and behavior, including depressive behavior. Antidepressants are the main drugs used for treatment of depression. We hypothesized that antidepressant treatment could modify gut microbiota which can partially mediate their antidepressant effects. Mice were chronically treated with one of five antidepressants (fluoxetine, escitalopram, venlafaxine, duloxetine or desipramine), and gut microbiota was analyzed, using 16s rRNA gene sequencing. After characterization of differences in the microbiota, chosen bacterial species were supplemented to vehicle and antidepressant-treated mice, and depressive-like behavior was assessed to determine bacterial effects. RNA-seq analysis was performed to determine effects of bacterial treatment in the brain. Antidepressants reduced richness and increased beta diversity of gut bacteria, compared to controls. At the genus level, antidepressants reduced abundances of Ruminococcus, Adlercreutzia, and an unclassified Alphaproteobacteria. To examine implications of the dysregulated bacteria, we chose one of antidepressants (duloxetine) and investigated if its antidepressive effects can be attenuated by simultaneous treatment with Ruminococcus flavefaciens or Adlercreutzia equolifaciens. Supplementation with R. flavefaciens diminished duloxetine-induced decrease in depressive-like behavior, while A. equolifaciens had no such effect. R. flavefaciens treatment induced changes in cortical gene expression, up-regulating genes involved in mitochondrial oxidative phosphorylation, while down-regulating genes involved in neuronal plasticity. Our results demonstrate that various types of antidepressants alter gut microbiota composition, and further implicate a role for R. flavefaciens in alleviating depressive-like behavior.
2019-04-05 | GSE129359 | GEO
Project description:Background: The goal of this study was to determine the transcriptional consequences of norepinephrine transporter (NET) gene deletion in noradrenergic neuron differentiation. The norepinephrine transporter (NET) is the target of powerful mind-altering substances, such as tricyclic antidepressants and the drug of abuse, cocaine. NET function in adult noradrenergic neurons of the peripheral and central nervous systems is that of a scavenger that internalizes norepinephrine from the synaptic cleft. By contrast, norepinephrine (NE) transport has a different role in embryogenesis. It promotes differentiation of neural crest cells and locus ceruleus progenitors into noradrenergic neurons, whereas NET inhibitors, such as the tricyclic antidepressant desipramine and the drug of abuse, cocaine, inhibit noradrenergic differentiation. While NET structure und regulation of NET function is well described, little is known about downstream targets of NE transport. Results: We have determined by long serial analysis of gene expression (LongSAGE) the gene expression profiles of in vitro differentiating wild type and norepinephrine transporter-deficient (NETKO) neural crest derivatives. Comparison analyses with the wild type library (GSM 105765) have identified a number of important differentially expressed genes, including genes relevant to noradrenergic neuron differentiation and to the phenotype of NETKO mice. Furthermore we have identified novel differentially expressed genes. Conclusions: Loss of NET function during embryonic development deregulates signaling pathways that are critically involved in neural crest formation and noradrenergic neuron differentiation. The library was constructed from total RNA of 60 neural crest culture at culture day 7. The neural tubes were dissected from E9.5 embryos that lack the norepinephrine transporter gene.
2008-06-23 | E-GEOD-11788 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE35751: Comparative analysis of S100a10-expressing cortical pyramidal cells and whole cortex GSE35758: Comparative analysis of S100a10 and Glt25d2 cortical pyramidal cells GSE35761: Effect of fluoxetine treatment on translational profiles of S100a10 cortical pyramidal cells GSE35763: Effect of fluoxetine treatment on translational profiles of Glt25d2 cortical pyramidal cells GSE35765: Effect of fluoxetine treatment on translational profiles of S100a10 cortical pyramidal cells in p11 KOs Refer to individual Series
2012-05-31 | E-GEOD-35766 | biostudies-arrayexpress