Cicardian regulation in rat liver
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE8988 | GEO | 2007/09/11
SECONDARY ACCESSION(S): PRJNA102455
REPOSITORIES: GEO
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Project description:In intact animals, time of drug administration may be an important factor influencing drug response. Our general goal seeks to incorporate circadian time into the study of corticosteroid regulated gene expression. This study is designed to examine fluctuations in gene expression in skeletal muscle within the 24 hour circadian cycle in normal animals. Circadian time is relevant to designing optimal corticosteroid dosing regimens. Since levels of endogenous steroid exhibit circadian fluctuations, it is our hypothesis that the expression of genes controlled by corticosteroids either directly or indirectly will also exhibit a circadian pattern in normal animals. Keywords: time series design
2007-09-11 | GSE8989 | GEO
Project description:In intact animals, time of drug administration may be an important factor influencing drug response. Our general goal seeks to incorporate circadian time into the study of corticosteroid regulated gene expression. This study is designed to examine fluctuations in gene expression in skeletal muscle within the 24 hour circadian cycle in normal animals. Circadian time is relevant to designing optimal corticosteroid dosing regimens. Since levels of endogenous steroid exhibit circadian fluctuations, it is our hypothesis that the expression of genes controlled by corticosteroids either directly or indirectly will also exhibit a circadian pattern in normal animals. Experiment Overall Design: Our previous studies examined changes in gene expression in response to corticosteroid treatment in adrenalectomized animals, where endogenous glucocorticoids are absent. This study is designed to examine baseline patterns of gene expression in normal animals within a 24 hour cycle. This data will be used in conjunction with future studies involving treatment of animals with corticosteroids at defined times within the circadian cycle. Fifty-four male normal Wistar rats (250-350 g body weight) were housed in a strictly controlled stress free environment with light:dark cycles of 12 hr:12hr. Three animals were sacrificed at each of 18 selected time points within the 24 hour cycle. RNA was prepared from gastrocnemius muscles for gene arrays. Time point designations reflect time after lights on in hours.
2008-06-17 | E-GEOD-8989 | biostudies-arrayexpress
Project description:In intact animals, time of drug administration may be an important factor influencing drug response. Our general goal seeks to incorporate circadian time into the study of corticosteroid regulated gene expression. Since levels of endogenous steroid exhibit circadian fluctuations, it is our hypothesis that the expression of genes controlled by corticosteroids either directly or indirectly, will also exhibit a circadian pattern in normal animals. Experiment Overall Design: This study is designed to examine fluctuations in gene expression in liver within the 24 hour circadian cycle in normal animals. Fifty-four male normal Wistar rats (250-350 g body weight) were housed in a strictly controlled stress free environment with light:dark cycles of 12 hr:12hr. Three animals were sacrificed at each of 18 selected time points within the 24 hour cycle. RNA was prepared from livers for gene arrays. Time point designations reflect time after lights on in hours.
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Project description:Disrupted circadian activity is associated with many neuropsychiatric disorders. A major coordinator of circadian biological systems is adrenal glucocorticoid secretion which exhibits a pronounced pre-awakening peak that regulates metabolic, immune, and cardiovascular processes, as well as mood and cognitive function. Loss of this circadian rhythm during corticosteroid therapy is often associated with memory impairment. Surprisingly the mechanisms that underlie this deficit are not understood. In this study, in rats, we report that circadian regulation of the hippocampal transcriptome integrates crucial functional networks that link corticosteroid-inducible gene regulation to synaptic plasticity processes via an intra-hippocampal circadian transcriptional clock. Further, these circadian hippocampal functions were significantly impacted by corticosteroid treatment delivered in a five day oral dosing treatment protocol. Rhythmic expression of the hippocampal transcriptome, as well as the circadian regulation of synaptic plasticity were misaligned with the natural light/dark circadian entraining cues, resulting in memory impairment in hippocampal-dependent behavior. These findings provide mechanistic insights into how the transcriptional clock machinery within the hippocampus is influenced by corticosteroid exposure, leading to adverse effects on critical hippocampal functions, as well as identifying a molecular basis for memory deficits in patients treated with long-acting synthetic corticosteroids.
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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.
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