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Response of multiple genes to a chronic dose of corticosteroids in rat muscles

ABSTRACT: Synthetic glucocorticoids are used therapeutically for a variety of conditions. Both the efficacy and toxicity of corticosteroids arise from their pharmacologically exaggerated effects on target and non-target tissues. For example, beneficial effects deriving from inhibition of the immune system are accompanied by toxic side effects that include hyperglycemia, dyslipidaemia, muscle wasting, fatty liver, and an increased risk of atherosclerosis. Our previous time series analyzing the gene expression responses following a single bolus dose of methylprednisolone (MPL) provided interesting insight into the genomic responses of liver, skeletal muscle and kidney to corticosteroids. One objective with such extensive gene array time series data is to cluster genes into groups with common mechanisms of regulation. These clusters can be used to construct biologically rational models of the cascade of events that result in broad systemic phenomena such as diabetes, with the ultimate aim of therapeutic intervention at specific steps within the cascade Keywords: Time-Series

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE5101 | GEO | 2006/06/19

SECONDARY ACCESSION(S): PRJNA95357

REPOSITORIES: GEO

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Response of multiple genes to a chronic dose of corticosteroids in rat muscles

Project description:Synthetic glucocorticoids are used therapeutically for a variety of conditions. Both the efficacy and toxicity of corticosteroids arise from their pharmacologically exaggerated effects on target and non-target tissues. For example, beneficial effects deriving from inhibition of the immune system are accompanied by toxic side effects that include hyperglycemia, dyslipidaemia, muscle wasting, fatty liver, and an increased risk of atherosclerosis. Our previous time series analyzing the gene expression responses following a single bolus dose of methylprednisolone (MPL) provided interesting insight into the genomic responses of liver, skeletal muscle and kidney to corticosteroids. One objective with such extensive gene array time series data is to cluster genes into groups with common mechanisms of regulation. These clusters can be used to construct biologically rational models of the cascade of events that result in broad systemic phenomena such as diabetes, with the ultimate aim of therapeutic intervention at specific steps within the cascade Keywords: Time-Series We analyze the two time series profiles with the intent of seeking ways to use the two profiles in tandem for clustering. The acute profiles were generated by sacrificing animals following a single acute dose of MP [7]. The time points were: 0.25, 0.5, 0.75, 1, 2, 4, 5, 5.5, 6, 7, 8, 12, 18, 30, 48 and, 72 hours after dosing. The chronic profiles were generated by implanting Alzet mini-osmotic pumps with a constant flow rate [8, 9]. Animals were sacrificed at 6, 10, 13, 18, 24, 36, 48, 72, 96 and 168 hr following implantation.

2006-06-19 | E-GEOD-5101 | biostudies-arrayexpress

Pharmacogenomic effect of corticosteroid in skeletal muscle

Project description:The aim of this project is to identify distinct temporal patterns of RNA expression in the skeletal muscle of rats following a bolus dose of the corticosteroid methylprednisolone. 51 RG_U34A chips were used over 17 time points. Keywords: other

2003-07-16 | GSE490 | GEO

Transcription profiling time series of the response of Rattus norvegicus liver to treatment with methylprednisolone

Project description:Summary: The liver is the major site of gluconeogenesis, fat processing and distribution, as well as drug and xenobiotic metabolism. Altered gene expression in the liver is centrally invovled in both the immuosuppressive and the energetic actions of corticosteroids. Hypothesis: That pharmacodynamics can be derived from expression profiling data. Specific Aim: The aim of this project is to identify distinct temporal patters of RNA expression in the liver of rats following a bolus dose of the corticosteroid methylprednisolone. 47 RG_U34A chips were used for 17 time points.

2007-10-10 | E-GEOD-487 | biostudies-arrayexpress

Transcription profiling time series of the Rattus norvegicus skeletal muscle response to treatment with the corticosteroid methylprednisolone

2007-10-10 | E-GEOD-490 | biostudies-arrayexpress

PGA Rat Liver Methylprednisolone

2003-07-16 | GSE487 | GEO

Transcriptomic effects of prenatal exposure to corticosteroids on synaptic transmission

Project description:Prenatal exposure to synthetic corticosteroids can significantly alter postnatal development through changes in neurotransmitters and their receptors, and thus having long-lasting behavioral effects. Some of these changes have been observed in animal experiments, others also in humans prenatally exposed to synthetic corticosteroids. Here, we focused on transcriptomic changes within the prefrontal cortex of female rats prenatally exposed to either betamethasone or saline. The transcriptome has been assessed by novel computational tools to determine complex changes that may have life-long effects on phenotype, i.e., behavior. We analyzed how composition, topology and modulatory networks of the genomic fabric of the dopaminergic, GABAergic, and glutamatergic synapse (the transcriptome of the most interconnected and stably expressed gene network responsible for specific transmission) are afected by the prenatal exposure to corticosteroids and postnatal ketamine-induced seizures. One sex (F) x two prenatal exposures (B = betamethasone, S = saline) x two postnatal treatments (K = ketamine, S = saline). Biological replicates: 4 FSS, 4 FBS, 4 FBK.

2016-01-09 | E-GEOD-76694 | biostudies-arrayexpress

Transcriptomic effects of prenatal exposure to corticosteroids on synaptic transmission

Project description:Prenatal exposure to synthetic corticosteroids can significantly alter postnatal development through changes in neurotransmitters and their receptors, and thus having long-lasting behavioral effects. Some of these changes have been observed in animal experiments, others also in humans prenatally exposed to synthetic corticosteroids. Here, we focused on transcriptomic changes within the prefrontal cortex of female rats prenatally exposed to either betamethasone or saline. The transcriptome has been assessed by novel computational tools to determine complex changes that may have life-long effects on phenotype, i.e., behavior. We analyzed how composition, topology and modulatory networks of the genomic fabric of the dopaminergic, GABAergic, and glutamatergic synapse (the transcriptome of the most interconnected and stably expressed gene network responsible for specific transmission) are affected by prenatal exposure to corticosteroids and postnatal ketamine/saline treated NMDA-induced seizures.

2016-01-09 | GSE76694 | GEO

Rat Kidney Methylprednisolone

Project description:Summary: To identify distinct temporal patterns of mRNA expression in the kidney of rats following a bolus dose of the corticosteroid methylprednisolone. Hypothesis: That prednisone pharmacodynamics can be derived from expression profiling data. Keywords: other

2004-09-02 | GSE1721 | GEO

Transcription profiling of rat kidney samples following treatment with the corticosteroid methylprednisolone over several time intervals

2007-09-13 | E-GEOD-1721 | biostudies-arrayexpress

Oral dosing for antenatal corticosteroids in the rhesus macaque

Project description:Purpose: Evaluated the transcriptional effects of an effective oral dosing of antental corticosteroids using betamethasone-phophate compared to the clinical treatment with the combination drug betamethasone-phosphate+betamethasone-acetate for fetal lung maturation. Methods: RNA-sequencing of the fetal hippocampus, liver and lung was done. Differential expression analysis was done using read counts. Results: There were no significant differences between oral Beta-P and the clinical treatment in the fetal hippocampus. Small differences were detected in the fetal lung associated with cellular proliferation and in the fetal liver. Conclusions: Oral betamethasone-phosphate is an effective oral treatment that does not cause toxic effect in the fetal brain despite the higher dose.

2019-09-25 | GSE131194 | GEO

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