Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Gene Changes in Hippocampus from Mice with Conditional Knockout of Hippocampal GR, MR, or both GR and MR

ABSTRACT: Glucocorticoids are primary stress hormones that have been implicated in the pathogenesis of cognitive impairments and psychiatric illnesses. The hippocampus expresses high levels of glucocorticoid (GR) and mineralocorticoid receptors (MR) which both bind glucocorticoids. However, the specific and cooperative roles played by GR and MR in mediating the direct actions of stress on the hippocampus are unknown. To elucidate the function of hippocampal GR and MR, we generated mice with conditional knockout of GR (GREmx1-cre), MR (MREmx1-cre), or both GR and MR (GRMREmx1-cre) in the hippocampus. Genome-wide microarrays were performed on RNA isolated from the whole hippocampus to 1) identify genes subject to regulation by GR alone, MR alone, or both GR and MR and 2) identify the genes responsible for the morphological and behavioral phenotypes observed in these mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE149625 | GEO | 2021/08/04

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Glucocorticoid and Mineralocorticoid Receptor Signaling have Sex-dependent and Independent Effects in Mouse Hippocampus

Project description:Many stress-related neuropsychiatric disorders display pronounced sex differences in their frequency and clinical symptoms. Glucocorticoids are primary stress hormones that have been implicated in the development of these disorders but whether they contribute to the observed sex bias is poorly understood. Glucocorticoids signal through two closely related nuclear receptors, the glucocorticoid (GR) and mineralocorticoid receptor (MR), that are both expressed at high levels in the hippocampus. To investigate the sex-dependent and independent actions of glucocorticoids in the hippocampus, we developed knockout mice lacking hippocampal GR (GREmx1-cre), MR (MREmx1-cre), or both GR and MR (GRMREmx1-cre). Genome-wide microarrays were performed on RNA isolated from the hippocampus of male and female flox control and knockout mice in order to 1) identify genes dysregulated in a sex-dependent and independent manner by a deficiency in GR, MR, or both GR and MR signaling and 2) identify the genes responsible for the sex-dependent and independent phenotypes observed in these mice.

2023-12-05 | GSE240873 | 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

Gene Changes in Hippocampus from Mice with Conditional Knockout of Hippocampal GR, MR, or both GR and MR

Project description:Gene Changes in Hippocampus from Mice with Conditional Knockout of Hippocampal GR, MR, or both GR and MR

| PRJNA629474 | ENA

Global Gene Changes in Hearts from CardioMRKO Mice

Project description:Heart failure is one of the leading causes of death in the Western world, and stress is increasingly associated with adverse cardiac outcomes. Glucocorticoids are primary stress hormones that regulate homeostasis through two closely related nuclear receptors, the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR). Cardiomyocytes express both receptors but little is known concerning their coordinated actions in heart physiology and pathology. To examine the in vivo function of glucocorticoid signaling in the heart, we generated mice with cardiomyocyte-specific deletion of GR (cardioGRKO), MR (cardioMRKO), or both GR and MR (cardioGRMRdKO). The cardioMRKO mice exhibited normal heart function whereas the cardioGRKO mice spontaneously developed cardiac hypertrophy and left ventricular systolic dysfunction. Surprisingly, the cardioGRMRdKO mice were protected from cardiac disease. Genome-wide microarrays were performed on isolated hearts from each mouse model to 1) identify genes subject to regulation by GR alone, MR alone, or both GR and MR and 2) identify the genes responsible for the cardiac pathology in the cardioGRKO mice and for the cardioprotection in the cardioGRMRdKO mice.

2019-04-17 | GSE95732 | GEO

Global Gene Changes in Hearts from CardioGRKO Mice

2019-04-17 | GSE95727 | GEO

Global Gene Changes in Hearts from CardioGRMRdKO Mice

2019-04-17 | GSE95719 | GEO

Mineralocorticoid receptor (MR) trans-activation of inflammatory AP-1 signaling: dependence on DNA sequence, MR conformation, and AP-1 family member expression

Project description:Mineralocorticoid receptor (MR) primarily promote cardiovascular inflammation by incompletely understood mechanisms. The differential effects of GR and MR on inflammatory signaling and their contextual dependencies are relevant to the design of next generation drugs with improved safety and efficacy While MR has been shown to weakly repress NFκB, its role in modulating AP-1 has not been established

2016-09-20 | GSE80276 | GEO

Glucocorticoid action in the hippocampus revealed by integrated genome-wide ChIP and RNA analysis [ChIP-seq]

Project description:Glucocorticoid hormones (GCs) play a critical role in physiological regulation and behavioural adaptation through mineralocorticoid (MR)- and glucocorticoid receptor (GR)-mediated actions in the hippocampus. We conducted genome-wide MR and GR ChIP-Seq studies on rat hippocampus to elucidate MR- and GR-regulated genes under physiological conditions like acute stress and circadian variation. Rat hippocampus tissue was collected under early morning baseline conditions, at 30 min after the start of a 15-min forced swim session (acute stress), or under late afternoon baseline conditions. We identified many genomic loci in which MR and/or GR binds following acute stress or due the circadian rise in GC secretion.

2021-07-10 | GSE126510 | GEO

Cardiac aldosterone and corticosterone regulated genes in mice with cardiomyocytes targeted mineralocorticoid receptor overexpression (MR-Cardio mice) and their controls (Ctrl mice)

Project description:Inappropriate mineralocorticoid receptor (MR) activation is involved in cardiac diseases. MR binds aldosterone, but also glucocorticoids; the identity of the ligand responsible for the deleterious effects of cardiac MR activation is still unclear. Mice overexpressing MR in cardiomyocytes (MR-Cardio) and their controls (Ctrl) were treated for 7 days with aldosterone or corticosterone and a whole genome microarray analysis was performed.

2017-09-01 | GSE33022 | GEO

Exploiting crosstalk between glucocorticoid and mineralocorticoid receptors enhances glucocorticoid-induced killing of multiple myeloma cells

Project description:Long-term glucocorticoid treatment in multiple myeloma is hampered by deleterious side effects. Glucocorticoids bind to the glucocorticoid receptor (GR), which is a crucial drug target because its activation triggers myeloma cell death. The mineralocorticoid receptor (MR) is a closely related nuclear receptor but its impact on glucocorticoid responsiveness in myeloma is unknown. Here we reveal a functional crosstalk between GR and 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 enhances Dex-induced cell killing in (primary) myeloma cells. The crosstalk is further evidenced by an endogenous interaction between GR and MR in myeloma cells that is ligand-inducible and by a distinctive gene expression profile. Our study demonstrates that GR-MR crosstalk is therapeutically relevant in myeloma and presents a glucocorticoid-based dose-reduction strategy that could diminish glucocorticoid-related side effects in patients.

2023-08-23 | GSE200313 | 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