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Genome-wide RNAseq of hippocampi from single time point (2 hours post 0.75 mg/mL corticosterone injection) in adrenalectomized rats

ABSTRACT: Genome-wide RNAseq of hippocampi from single time point (2 hours post 0.75 mg/mL corticosterone injection) in adrenalectomized rats

PROVIDER: PRJNA929468 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23270406.fastq.gz	Fastqsanger.gz
	SRR23270407.fastq.gz	Fastqsanger.gz
	SRR23270408.fastq.gz	Fastqsanger.gz
	SRR23270409.fastq.gz	Fastqsanger.gz
	SRR23270410.fastq.gz	Fastqsanger.gz

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Genome-wide RNAseq of hippocampi from single time point (2 hours post 0.75 mg/mL corticosterone injection) in adrenalectomized rats

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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Sex-Dependent Changes of miRNA Levels in the Hippocampus of Adrenalectomized Rats Following Acute Corticosterone Administration

Project description:We explored sex-biased effects of the primary stress glucocorticoid hormone corticosterone on the miRNA expression profile in the rat hippocampus. Adult adrenalectomized (ADX) female and male rats received a single corticosterone (10 mg/kg) or vehicle injection and after 6 h, hippocampi were collected for miRNA, mRNA and Western blot analyses. miRNA profiling microarrays showed a basal sex-biased miRNA profile in ADX rat hippocampi. Additionally, acute corticosterone administration triggered a sex-biased differential expression of miRNAs derived from genes located in several chromosomes and clusters on the X and 6 chromosomes. Putative promoter analysis unveiled that most corticosterone-responsive miRNA genes contained motifs for either direct or indirect glucocorticoid actions in both sexes. The evaluation of transcription factors indicated that almost 50 % of miRNA genes sensitive to corticosterone in both sexes was under glucocorticoid receptor regulation. Transcription factor-miRNA regulatory network analyses identified several transcription factors that regulate, activate or repress miRNA expression. Validated target mRNA analysis of corticosterone-responsive miRNAs showed a more complex miRNA-mRNA interaction network in males compared to females. Enrichment analysis revealed that several hippocampal-relevant pathways were affected in both sexes, such as neurogenesis and neurotrophin signaling. The evaluation of selected miRNA targets from these pathways displayed a strong sex difference in the hippocampus of ADX-vehicle rats. Corticosterone treatment did not change the levels of the miRNA targets and their corresponding tested proteins. Our data indicate that corticosterone exerts a sex-biased effect on hippocampal miRNA expression, which may engage in sculpting the basal sex differences observed at higher levels of hippocampal functioning.

2021-08-01 | GSE181268 | GEO

Adrenalectomy plus corticosterone treatment, rat hippocampal RNA-seq

Project description:Male Sprague-Dawley rats 8 weeks old, were adrenalectomized, treated with 300ug/kg corticosterone or vehicle 3 days after surgery then sacrificed 1 hour later. Hippocampi were removed and RNA extracted and processed for sequencing at the Massachusetts General Hospital Nex-Generation Sequening Core. Includes 6 cort treated and 6 control biological replicates

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Ventral hippocampal transcriptome analysis after acute corticosterone exposure.

Project description:Aim: We investigated the effect of acute corticosterone exposure 3 hours after subcutaneous injection on the ventral hippocampus transcriptome. Methods: Adult male mice were used in the experiment. Mice were sacrificed 3 hours after corticosterone (3mg/kg) of vehicle injection and the ventral hippocampus was dissected and snap-frozen. Subsequently, total RNA was isolated and send for 100bp paired-end sequencing by BGI.

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Adrenalectomy plus corticosterone treatment, rat hippocampal RNA-seq

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Project description:ObjectiveThe present study compared the bioavailability of subcutaneous (s.c.) Chemi Enoxaparin with Clexane (80 mg/0.8 mL) under fasting conditions in healthy subjects.Materials and methodsThis study was an open-label, randomized, single-dose, two-treatment period crossover study. We included healthy male and female subjects aged 18 - 55 years with a body mass index of 18 - 30 kg/m2. The primary pharmacodynamic endpoints were anti-FIIa and anti-FXa activity. Bioequivalence was achieved when the 95% confidence interval (CI) for the geometric means of Cmax and AUC0-t was between 80.00 and 125.00%.Results47 subjects were randomized for the treatment sequences. The 95% CI of the ratios of the geometric least squared means of anti-FXa activity was 96.28 - 102.65 IU/mL for Cmax and 100.67 - 105.15 h×IU/mL for the AUC0-t of Chemi Enoxaparin compared with those of Clexane, and for anti-FIIa activity, they were 86.65 - 96.73 IU/mL for the Cmax and 87.72 - 97.25 h×IU/mL AUC0-t, which met the criterion for bioequivalence. The number of subjects reporting at least 1 treatment-emergent adverse event (TEAE) was low, mostly of mild severity, and similar for both compounds.ConclusionChemi enoxaparin is bioequivalent to the reference enoxaparin, and both compounds show similar tolerability and safety profiles.

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Gene expression of 7 day combinatorial yohimbine and imipramine treated rat hippocampi

Project description:Rats treated on 7 consecutive days with either 2 injections of vehicle (Ctl) (DMSO for yohimbine, saline for imipramine) or Y+I (2mg/kg Yohimbine + 20mg/kg Imipramine) were sacrificed 2 hours post the last injection and their hippocampi used for gene expression analysis.

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