Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Glucocorticoid resistance during chronic social stress in mice: RNA-seq of prefrontal cortex

ABSTRACT: Chronic stress often leads to the development of various psychopathologies and is usually associated with a change in the function of the HPA axis. An elevated level of glucocorticoid (GC) hormones in the blood initially causes an acute reaction of the body, which subsequently fades, even with continued stimulation with glucocorticoids. It is known that the degree of resistance to elevated hormone levels can affect the effectiveness of therapy in the treatment of stress-induced psychopathologies. In order to identify the molecular basis for the formation of GC resistance, we analyzed the effect of chronic social stress on the transcriptome of the prefrontal cortex in an experimental model of depression. We assessed the level of gene expression in the prefrontal cortex of the control C57BL/6 mice and mice with stress experience for 30 days, both in the basal state and with additional stimulation with dexamethasone. The introduction of dexamethasone made it possible to simulate the situation of an increase in the level of glucocorticoids and activation of the glucocorticoid receptor.

ORGANISM(S): Mus musculus

PROVIDER: GSE330674 | GEO | 2026/05/13

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

DiffBrainNet: A combined resource of differential networks and differential expression to analyze transcriptomic responses to glucocorticoids in 8 mouse brain regions.

Project description:Activation of the stress-axis is an important component of the biology of stress-related psychiatric disorders. The main stress hormones of the mammalian body are glucocorticoids. Glucocorticoids bind to glucocorticoid receptors and act as transcription factors modulating the transcriptional landscape. Dexamethasone is a synthetic glucocorticoid that is used to activate the glucocorticoid receptors and thus mimic some aspects of the altered transcriptomic landscape that are associated with stress-related psychiatric disorders. We used intraperitoneal dexamethasone of C57Bl/6 mice and analyzed the transcriptional landscape of 8 brain regions: the prefrontal cortex, the amygdala, the paraventricular nucleus of the hypothalamus, the dorsal and ventral Cornu ammonis 1, the dorsal and ventral dentate gyrus and the cerebellar cortex. We implored differential expression in combination with differential network analysis to study the transcriptomic responses to dexamethasone in each brain region. We found that differential networks and differential expression explain distinct but complementary aspects of the responses to the stimulus and that network analysis can unravel underlying biological mechanisms that are hidden at the gene level. Using our dataset we could analyze the molecular connectivity of Tcf4, an important psychiatric risk gene, at the baseline and differential levels. We provide an analysis framework and a resource for the study of the transcriptional landscape of 8 mouse brain regions at baseline, dexamethasone-treated and differential levels, called DiffBrainNet (http://134.76.24.68/app/diffbrainnet), that can be used pinpoint molecular pathways important for the basic functioning and response to glucocorticoids in a brain-region specific manner.

2022-04-15 | GSE190712 | GEO

Ligand-dependent genomic function of glucocorticoid receptor in triple-negative breast cancer

Project description:Glucocorticoids (GC) have been widely used as coadjuvants in the treatment of solid tumors, but GC treatment may be associated with poor pharmacotherapeutic response and/or prognosis. The genomic action of GC in these tumors is largely unknown. Here we find that dexamethasone (Dex, a synthetic GC) regulated genes in triple-negative breast cancer (TNBC) cells are associated with drug resistance. Importantly, these GC-regulated genes are aberrantly expressed in TNBC patients and associated with unfavorable clinical outcomes. Interestingly, in TNBC cells, Compound A (CpdA, a selective GR modulator) only regulates a small number of genes not involved in carcinogenesis and therapy resistance. Mechanistic studies using a ChIP-exo approach reveal that Dex- but not CpdA-liganded glucocorticoid receptor (GR) binds to a single glucocorticoid response element (GRE), which drives the expression of pro-tumorigenic genes. Our data suggest that development of safe coadjuvant therapy should consider the distinct genomic function between Dex- and CpdA-liganded GR. To study GR-regulated genes and define GRE in human genome, RNA-seq and GR ChIP-exo are performed in MDA-MB-231 cells before/after dex and CpdA stimulation. Each experiment includes two replicates.

2015-09-18 | E-GEOD-56022 | biostudies-arrayexpress

CCR1 inhibition sensitizes multiple myeloma cells to glucocorticoid therapy

Project description:One of the cornerstone drugs in the treatment of multiple myeloma (MM) are glucocorticoids. Because MM cells hijack the bone marrow microenvironment to obtain growth and survival signals, resistance to glucocorticoid-induced apoptosis emerges, yet, the underlying mechanisms remain poorly characterized. Here we identify that the chemokine receptor CCR1 together with its main ligand CCL3, plays a pivotal role in reducing glucocorticoid sensitivity of MM cells. We show that blocking of CCR1 signalling with the antagonist BX471 enhances the anti-MM effects of the glucorticoid dexamethasone in several MM cell lines, primary patient material and in a myeloma xenograft mouse model. Mechanistically, the drug combination shifts the balance between pro- and antiapoptotic proteins towards apoptosis and deregulates lysosomal proteins. We further find that the glucocorticoid-induced downregulation of CCR1 mRNA and protein is blunted in a glucocorticoid-resistance onset model. Finally, we demonstrate that CCR1 inhibition partially reverses GC-resistance, hereby offering a viable glucocorticoid resensitization strategy for MM treatment.

2025-06-18 | PXD055337 | Pride

Expression data from mouse adrenals during recovery after dexamethasone treatment

Project description:Long-term pharmacological glucocorticoid therapy causes atrophy and hypofunction of the adrenal cortex. Following glucocorticoids withdrawal, a functional and anatomic regeneration take place, whose cellular and molecular mechanisms are poorly understood We used microarrays to detail the gene expression changes occurring during adrenal regeneration following administration of dexamethasone

2017-12-06 | GSE107715 | GEO

Crosstalk between the glucocorticoid and mineralocorticoid receptor boosts glucocorticoid-induced killing of multiple myeloma cells

Project description:The glucocorticoid receptor (GR) is a crucial drug target in multiple myeloma as its activation with glucocorticoids effectively triggers myeloma cell death. However, as high-dose glucocorticoids are also associated with deleterious side effects, novel approaches are urgently needed to improve GR’s action in myeloma. Here we reveal a functional crosstalk between GR and the mineralocorticoid receptor (MR) that culminates in improved myeloma cell killing. We show that the GR agonist Dexamethasone (Dex) downregulates MR levels in a GR-dependent way in myeloma cells. Co-treatment of Dex with the MR antagonist Spironolactone (Spi) enhances Dex-induced cell killing in primary, newly diagnosed GC-sensitive myeloma cells, while in a relapsed GC-resistant setting, Spi alone induces distinct myeloma cell killing. On a mechanistic level, we find that a GR-MR crosstalk is arising from an endogenous interaction between GR and MR in myeloma cells. Quantitative dimerization assays show that Spi reduces Dex-induced GR-MR heterodimerization and completely abolishes Dex-induced MR MR homodimerization but leaves GR-GR homodimerization intact. Unbiased transcriptomics further reveals that c-myc and many of its target genes are downregulated most by Dex and Spi combined, while proteomics analyses identify that several metabolic hallmarks are modulated most by this combination treatment. Finally, we identified a subset of Dex+Spi downregulated genes and proteins that may predict prognosis in the CoMMpass patient cohort. Our study demonstrates that GR-MR crosstalk is therapeutically relevant in myeloma as it provides novel strategies towards glucocorticoid-based dose-reduction.

2023-10-24 | PXD043635 | Pride

Transcriptional response in acute lymphoblastic leukaemia cells to bone marrow microenvironment

Project description:Glucocorticoids (GCs) and topoisomerase II inhibitors are used in the treatment of acute lymphoblastic leukaemia (ALL) due to their ability to induce cell death in lymphoid cells. GC-induced apoptosis is mediated by the glucocorticoid receptor (GR), whereas topoisomerase II inhibitors cause DNA damage and activate sensors of DNA damage including the tumour suppressor p53. In order to shed light on the role of the microenvironment in cell death and identify determinants of drug sensitivity we performed transcriptomic analysis in ALL cells treated with the synthetic glucocorticoid dexamethasone, and the topoisomerase II inhibitor etoposide combined with bone marrow-derived conditioned media (CM).

2017-08-30 | E-MTAB-4761 | biostudies-arrayexpress

Expression data from a 24h time series of dexamethasone treatment for mouse bone marrow derived macrophages

Project description:Macrophages are amongst the major targets of glucocorticoids (GC) as therapeutic anti-inflammatory agents. Here we show that GC treatment of mouse and human macrophages initiates a cascade of induced gene expression including many anti-inflammatory genes. Inducible binding of the glucocorticoid receptor (GR) was detected at candidate enhancers in the vicinity of induced genes in both species and this was strongly associated with canonical GR binding motifs. However, the sets of inducible genes, the candidate enhancers, and the GR motifs within them, were highly-divergent between the two species. 3 biological replicates of a 6 point time series for the transcriptional response to dexamethasone 100nM

2015-12-17 | E-GEOD-61879 | biostudies-arrayexpress

Preclinical analysis of the gamma secretase inhibitor PF-030840214 in combination with glucocorticoids in T-cell acute lymphoblastic leukemia

Project description:T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic cancer frequently associated with activating mutations in NOTCH1. Early studies identified NOTCH1 as an attractive therapeutic target for the treatment of T-ALL through the use of gamma-secretase inhibitors (GSIs). Here, we characterized the interaction between PF-03084014, a clinically-relevant GSI, and dexamethasone in preclinical models of glucocorticoid-resistant T-ALL. Combination treatment of the GSI PF-03084014 with glucocorticoids induced a synergistic antileukemic effect in human T-ALL cell lines and primary human T-ALL patient samples. Molecular characterization of the response to PF-03084014 plus glucocorticoids through gene expression profiling revealed transcriptional upregulation of the glucocorticoid receptor as the mechanism mediating the enhanced glucocorticoid response. Moreover, treatment with PF-03084014 and glucocorticoids in combination was highly efficacious in vivo, with enhanced reduction of tumor burden in a xenograft model of T-ALL. Finally, glucocorticoid treatment was highly effective at reversing PF-03084014-induced gastrointestinal toxicity via inhibition of goblet cell metaplasia. These results suggest that combination of PF-03084014 treatment with glucocorticoids may be well-tolerated and highly active for the treatment of glucorticoid-resistant T-ALL. Duplicate samples of the CUTLL1 T-ALL cell line were treated with vehicle only (DMSO), the gamma-secretase inhibitor PF-03084014 (1 microM), dexamethasone (1 microM), or PF-03084014 (1 microM). plus dexamethasone (1 microM) for 48 hours. Gene expression profiling was analyzed to identify gene expression signatures assocuated with glucocorticoid treatment (dexamethasone), inhibition of NOTCH1 by gamma secretase inhibitor (PF-03084014) or the combination of both treatments.

2011-11-09 | E-GEOD-33562 | biostudies-arrayexpress

Comparative analysis of gene expression profiles in lymphoma cells after treatment by Dexamethasone or CpdA

Project description:The project is directed to the development of selective glucocorticoid receptor agonists for anticancer therapy. Glucocorticoids (GC) are widely used in treatment of many types of cancer due to its ability to induce apoptosis in malignant cells (in blood cancer therapy) and to prevent nausea and emesis (in the chemotherapy of solid tumors). However, severe dose-limiting side effects occur, including osteoporosis, muscle wasting, diabetes and other metabolic complications. Both beneficial and harmful effects of glucocorticoids are due to selective activation or repression of particular genes by glucocorticoid receptor (GR). GR regulates gene expression via transactivation that requires GR homodimer binding to gene promoters and transrepression mediated via negative interaction between GR and other transcription factors as well as binding with negative glucocorticoid response elements (nGRE) in genes. GR transactivation is linked to metabolic side effects, while GR transrepression underlies glucocorticoid therapeutic action. Novel selective GR agonist Compound A (CpdA) prevents GR dimerization and transactivation, specifically activates GR transrepression, and has fewer side effects compared to glucocorticoids. Here we compare the gene expression profiles in lymphoma cells treated with glucocorticoid Dexamethasone (Dex) or CpdA

2015-07-21 | GSE71102 | GEO

Comparative analysis of gene expression profiles in prostate cancer cells after treatment by Dexamethasone or CpdA

Project description:The project is directed to the development of selective glucocorticoid receptor agonists for anticancer therapy. Glucocorticoids (GC) are widely used in treatment of many types of cancer due to its ability to induce apoptosis in malignant cells (in blood cancer therapy) and to prevent nausea and emesis (in the chemotherapy of solid tumors). However, severe dose-limiting side effects occur, including osteoporosis, muscle wasting, diabetes and other metabolic complications. Both beneficial and harmful effects of glucocorticoids are due to selective activation or repression of particular genes by glucocorticoid receptor (GR). GR regulates gene expression via transactivation that requires GR homodimer binding to gene promoters and transrepression mediated via negative interaction between GR and other transcription factors as well as binding with negative glucocorticoid response elements (nGRE) in genes. GR transactivation is linked to metabolic side effects, while GR transrepression underlies glucocorticoid therapeutic action. Novel selective GR agonist Compound A (CpdA) prevents GR dimerization and transactivation, specifically activates GR transrepression, and has fewer side effects compared to glucocorticoids. Here we compare the gene expression profiles in prostate cancer cells treated with glucocorticoid Dexamethasone (Dex) or CpdA

2015-07-21 | GSE71099 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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