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| Status |
Public on Feb 12, 2023 |
| Title |
Genome-wide RNAseq of hippocampi from single time point (2 hours post 0.75 mg/mL corticosterone injection) in adrenalectomized rats |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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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| Overall design |
Hippocampus RNA expression from adult adrenalectomized vehicle and corticosterone treated rats at zeitgeiber (ZT) 2
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| Contributor(s) |
Birnie MT, Lightman SL, Conway-Campbell BL |
| Citation(s) |
37023133 |
| |
| Submission date |
Jan 30, 2023 |
| Last update date |
May 03, 2023 |
| Contact name |
Matthew Birnie |
| E-mail(s) |
mbirnie@uci.edu
|
| Organization name |
University of California-Irvine
|
| Street address |
Health Sciences Road
|
| City |
Irvine |
| ZIP/Postal code |
92617 |
| Country |
USA |
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| Platforms (1) |
| GPL18694 |
Illumina HiSeq 2500 (Rattus norvegicus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA929468 |
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