Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Gene expression profiling of early-activated targets of antidepressants in glia cells

ABSTRACT: 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.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE89873 | GEO | 2016/11/16

SECONDARY ACCESSION(S): PRJNA353626

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Antidepressants affect gut microbiota and Ruminococcus flavefaciens is able to abolish their effects on depressive-like behavior

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

Effects of chronic desipramine treatment on hippocampal transcriptome in mice differing in response to antidepressants

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

Effects of chronic desipramine treatment on hippocampal transcriptome in mice differing in response to antidepressants

2011-02-26 | GSE27532 | GEO

Bacteria proteomics under antidepressants exposure

Project description:This project conducted proteomics on A.baylyi ADP1, E. coli K12 and P. putita KT2440 after treated with a few commonly-prescribed antidepressant (duloxetine, sertraline, fluoxetine, bupropion, escitalopram and agomelatine). The results with help to reveal how those antidepressants can promote the transfer of antibiotic resistance genes in those treated bacteria.

2024-01-26 | PXD028020 | Pride

RGS9-2-controlled adaptations in the striatum determine the onset of action and eficacy of antidepressants in neuropathic pain states

Project description:The striatal protein Regulator of G protein signaling-2 (RGS9-2) plays a key modulatory role in opioid, monoamine and other GPCR responses. Here, we use the murine spared-nerve injury model of neuropathic pain to investigate the mechanism by which RGS9-2 in the nucleus accumbens (NAc), a brain region involved in mood reward and motivation, modulates the actions of tricyclic antidepressants (TCAs). Prevention of RGS9-2 action in the NAc increases the efficacy of the TCA desipramine and dramatically accelerates its onset of action. By controlling the activation of effector molecules by G protein a and bg subunits, RGS9-2 affects several protein interactions, phosphoprotein levels, and the function of the epigenetic modifier histone deacetylase 5 (HDAC5), that are important for TCA responsiveness. Furthermore, information from RNA-seq analysis reveals that RGS9-2 in the NAc affects the expression of many genes known to be involved in nociception, analgesia and antidepressant drug actions. Our findings provide novel information on NAc-specific cellular mechanisms that mediate the actions of TCAs in neuropathic pain states. The RNAseq study was designed in order to reveal the impact of RGS9-2 on gene regulation in the Nucleus Accumbens under neuropathic pain and antidepressant treatment conditions. A total of 18 samples was used, coprising 6 different groups , and each group consisted of three different biological replicates.

2015-08-25 | E-GEOD-71527 | biostudies-arrayexpress

Epigenetic effects of antidepressants to neuroprotective genes in neuronal cultured cells

Project description:Antidepressants are widely used for treatment of depression. Imipramine, a typical antidepressant, is recently known to have an effect to restore the expression of brain-derived neurotrophic factor gene, which is decreased in depressed patients, by increasing histone acetylation. However, it is largely unknown whether other antidepressants have similar epigenetic effects to change gene expression. To address this question, we examined the effect of five antidepressants (imipramine, citalopram, duloxetine, amitriptyline, mirtazapine) on expression of genes associated with mental and neurodegenetative disorders. We found that 48-hour treatment with imipramine, citalopram, amitriptyline, mirtazapine, but not duloxetine, caused a large number of differentially expressed genes in primary neocortical neurons in mice. Focused on genes relating to neural protection and neuroplasticity, we discovered that amitriptyline not only enhanced the expression of atf3 and cox2 by increasing histone H3 Lys4 trimethylation (H3K4me3), but also protected neurons against oxygen-glucose deprivation and staurosporine-induced apoptosis. Our study will shed a new insight in understanding of the molecular and epigenetic mechanism of antidepressants. Mouse primary neuronal cultures were used to evaluate 48 hour effects of antidepressants. Briefly, cultured neurons at day in vitro 3 (DIV3) were treated with 5ÂµM imipramine, 10 ÂµM citalopram, 0.1 ÂµM duloxetine, 5 ÂµM amitriptylline, 50 ÂµM mirtazepine. These cultures were harvested after 48 hours (DIV5).

2015-01-30 | E-GEOD-63005 | biostudies-arrayexpress

Epigenetic effects of antidepressants to neuroprotective genes in neuronal cultured cells

2015-01-30 | GSE63005 | GEO

RGS9-2-controlled adaptations in the striatum determine the onset of action and eficacy of antidepressants in neuropathic pain states

2015-08-25 | GSE71527 | GEO

Acid sphingomyelinase deactivation post-ischemia/ reperfusion promotes cerebral angiogenesis and brain remodeling via small extracellular vesiclesAcid sphingomyelinase deactivation post-ischemia/ reperfusion promotes cerebral angiogenesis and brain remodeling via small extracellular vesicles

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

Tianeptine promotes lasting antiallodynic effects in a mouse model of neuropathic pain

Project description:Tricyclic antidepressants (TCAs), such as desipramine (DMI), are effective at managing neuropathic pain symptoms but often take several weeks to become effective and also lead to considerable side effects. Tianeptine (TIAN) is an atypical antidepressant that activates the mu-opioid receptor but does not produce analgesic tolerance or withdrawal in mice, nor euphoria in humans, at clinically-relevant doses. Here, we evaluate the efficacy of TIAN at persistently alleviating mechanical allodynia in the spared nerve injury (SNI) model of neuropathic pain, even well after drug clearance. After finding an accelerated onset of antiallodynic action compared to DMI, we used genetically modified mice to gain insight into RGS protein-associated pathways that modulate the efficacy of TIAN relative to DMI in models of neuropathic pain. Because we observed similar behavioral responses to both TIAN and DMI treatment in RGS4, RGSz1, and RGS9 knockout mice, we performed RNA sequencing on the NAc of TIAN- and DMI-treated mice after prolonged SNI to further clarify potential mechanisms underlying TIANs faster therapeutic actions. Our bioinformatic analysis revealed distinct transcriptomic signatures between the two drugs, with TIAN more directly reversing SNI-induced differentially expressed genes, and further predicted several upstream regulators that may be implicated in onset of action. This new understanding of the molecular pathways underlying TIAN action may enable the development of novel and more efficacious pharmacological approaches for the management of neuropathic pain.

2023-07-24 | GSE237896 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data