Control of bladder peripheral clock and diurnal micturition pattern by glucocorticoids
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE205971 | GEO | 2022/06/16
REPOSITORIES: GEO
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Project description:Three groups of Wistar rats with different manipulated levels of corticosterone were used to identify corticosteroid-responsive genes in hippocampus: 1. rats were adrenalectomised (ADX) 2. In addition to ADX these rats were implanted with a subcutaneous pellet containing 20 mg corticosterone and 80% cholesterol (ADX + low CORT) 3. In addition to ADX and implantation of a corticosterone pellet, these rats received a subcutaneous injection with corticosterone (1 mg/kg bodyweight) three hours prior to decapitation ((ADX + low CORT) + acute high CORT). All 3 groups of rats were decapitated three days after ADX and their hippocampus was isolated. Hippocampal RNA from 6 rats per group was pooled and used as input material for the SAGE libraries. Keywords: parallel sample
2003-10-30 | E-GEOD-787 | biostudies-arrayexpress
Project description:Although glucocorticoids (GCs) are known to exert numerous effects in the hippocampus, their chronic regulatory functions remain poorly understood. Moreover, evidence is inconsistent regarding the longstanding hypothesis that chronic GC exposure promotes brain aging/Alzheimer's disease. Here, we adrenalectomized male F344 rats at 15-months-of-age, maintained them for 3 months with implanted corticosterone (CORT) pellets producing low or intermediate (glucocorticoid-receptor (GR)-activating) blood levels of CORT, and performed microarray/pathway analyses in hippocampal CA1. We defined the chronic GC-dependent transcriptome as 393 genes that exhibited differential expression between Intermediate- and Low-CORT groups. Short-term CORT (4 days) did not recapitulate this transcriptome. Functional processes/pathways overrepresented by chronic CORT-upregulated genes included learning/plasticity, differentiation, glucose metabolism and cholesterol biosynthesis, whereas processes overrepresented by CORT-downregulated genes included inflammatory/immune/glial responses and extracellular structure. These profiles indicate that GCs chronically activate neuronal/metabolic processes while coordinately repressing a glial axis of reactivity/inflammation. We then compared the GC-transcriptome with a previously-defined hippocampal aging transcriptome, revealing a high proportion of common genes. Although CORT and aging moved expression of some common genes in the same-direction, the majority were shifted in opposite directions by CORT and aging (e.g., glial inflammatory genes downregulated by CORT are upregulated with aging). These results contradict the hypothesis that GCs simply promote brain aging, and also suggest that the opposite-direction shifts during aging reflect resistance to CORT regulation. Therefore, we propose a new model in which aging-related GC resistance develops in some target pathways while GC overstimulation develops in others, together generating much of the brain aging phenotype. Forty male Fischer 344 rats aged 14-15 months (late mid-age) were either sham operated (n=10) or adrenalectomized (n=30) at Harlan, Inc. (Indianapolis) and shipped to University of Kentucky 7-10 d after surgery. Animals were allowed to acclimate for 2 weeks after receipt prior to pellet-implant and were provided with food and water ad lib. Adrenalectomized (ADX) animals were maintained on drinking water containing isotonic saline with 1% sucrose, and also given supplemental feed mash (standard chow mixed with water and warmed) and apple chunks, as well as subcutaneous injections of 1.25 mg corticosterone sulfate (Solu-DeltaCort, Pfizer). During pellet-implant surgery, subjects were anesthetized with isoflurane, placed on a warming pad, and a 3 cm2 area on the animal's flank was shaved and sterilized. A 1-cm incision was made through the skin to form a subcutaneous pocket. Each sham animal received an inert pellet. ADX animals were divided into two groups, low-dose animals (n = 20) received one 25 mg CORT pellet and intermediate-dose animals (n = 10) received one 200 mg CORT pellet (slow release pellets, Innovative Research of America, Sarasota, FL). Incisions were closed with wound clips (removed after 7-10 days). Following implant surgery, subjects were housed singly for 3 months prior to euthanasia at age 18 months. Low-dose animals continued to receive saline/ sucrose drinking water, but other supplementation (food mash, Solu-Delta CORT, apple chunks) was discontinued. One ADX animal was removed from the study for declining health. During the twelfth week, just prior to study termination, half of the ADX low-dose CORT subjects were given a short-term, high-dose regimen consisting of 4 daily IP injections of 5mg/d CORT (considered a relatively high dose- Makino et al., 1995). All animals were killed between 8 and 10 AM on the last two days of the study. After deep CO2 anesthesia and decapitation, trunk blood was collected for CORT radioimmunoassay and hippocampal CA1 brain tissue was dissected as described previously (Blalock et al., 2003) for microarray analysis (see below). Final treatment groups consisted of: 1) Sham (intact) control, 2) Low-CORT (ADX), 3) Intermediate-CORT (ADX), and 4) Low-CORT (ADX) + short-term high-dose injected (n=9-10/group).
2013-07-22 | E-GEOD-37618 | biostudies-arrayexpress
Project description:Three groups of Wistar rats with different manipulated levels of corticosterone were used to identify corticosteroid-responsive genes in hippocampus: 1. rats were adrenalectomised (ADX) 2. In addition to ADX these rats were implanted with a subcutaneous pellet containing 20 mg corticosterone and 80% cholesterol (ADX + low CORT) 3. In addition to ADX and implantation of a corticosterone pellet, these rats received a subcutaneous injection with corticosterone (1 mg/kg bodyweight) three hours prior to decapitation ((ADX + low CORT) + acute high CORT). All 3 groups of rats were decapitated three days after ADX and their hippocampus was isolated. Hippocampal RNA from 6 rats per group was pooled and used as input material for the SAGE libraries. Keywords: parallel sample
2003-10-31 | GSE787 | GEO
Project description:Purpose: we sought to search for genes that are transcribed or repressed in a glucocorticoid (GC)-dependent manner in a hypothalamic region containing the paraventricular nucleus of the hypothalamus (PVH), thereby unraveling mechanisms underlying GC-induced neuroendocrine and autonomic regulation. Methods: we employed unbiased quantification of the abundance of DNA transcripts provided by RNA-seq in the PVH region of male rats and identified genes whose expression is enhanced or suppressed by the 12-day exposure to a high dose of corticosterone (Cort) by Cort implant (12-day high Cort) or deprivation of corticoids for 7 days [7-day adrenalectomy (ADX)] (Experiment 1), as well as by acute Cort increase (Experiment 2). Sham-ADX animals served as controls in Experiment 1. In Experiment 2, rats underwent ADX and supplemented with Cort in drinking water. The animals were decapitated at 1 h [acute Cort (1) 1 h] or 3 h [acute Cort (1) 3 h] following injection of HBC Cort (1 mg), a dose shown to elicit plasma Cort surge comparable to that during acute stress. A group of rats without Cort injection served as controls (ADX + Cort suppl). Differential expression was calculated as fold-changes in gene expression [measured as fragments per kilobase of exon per million reads mapped (FPKM)]. The Benjamini & Hochberg method was applied to correct the unavoidable false positive data ensued from the multiple tests, and a q-value was calculated as the false discovery rate-adjusted p-value. The q-value < 0.05 was used as the cut-off criterion. Pearson’s correlation analysis was carried out for grouping genes that showed similar expression patterns. qRT–PCR validation was performed using Power SYBR Green PCR mix. Semi-quantitative in situ hybridization was carried out using 35S-labeled cRNA probes. Results: some canonical GC target genes, among others of a broad functional spectrum, were upregulated prominently by 12-day high Cort. Crh was upregulated or downregulated most prominently by either 7-day ADX or 12-day high Cort, emphasizing the recognized feedback effects of GC on the hypothalamic-pituitary-adrenal (HPA) axis. Concomitant changes in Avp and Aplnr expression are likely to contribute to HPA repression. In keeping with the pleotropic cellular actions of GCs, 7-day ADX downregulated numerous genes of a broad functional spectrum. The transcriptome response signature differed markedly between acute Cort injection and 12-day high Cort. Remarkably, 6 immediate early genes, Bsx, Egr1, Fos, Fosb, Junb, and Nr4a3, were upregulated at 1 h after Cort injection, and the changes were confirmed by qRTPCR and semi-quantitative in situ hybridization. Conclusions: the present study uncovered a broad spectrum of Cort-responsive genes, potentially involved in the regulation of the HPA-axis, as well as other neuroendocrine and pre-autonomic functions of the PVH.
2018-09-15 | GSE120002 | GEO
Project description:The circadian rhythm controls timed choreography of gene expression to maintain normal cell physiology and metabolism. The predominant regulatory mechanism of the circadian rhythm is a transcriptional negative feedback loop that facilitates, and is facilitated by, circadian-regulated facultative heterochromatin. The long-term consequence of disrupted diurnal rhythm, or mutations in core clock genes, cause accelerated aging and an increased incidence in age-related diseases. To understand chromatin dynamics underlying age-related changes to circadian transcription, we performed a combined RNA-seq and ChIP-seq at two diurnal time-points for three different age groups. Our analysis focused on uncovering relationships between long non-coding RNA (lncRNA) and age-related changes to heterochromatin. We determined that the core clock genes maintain rhythmic expression regardless of age, but circadian output, including numerous lncRNAs, changes dramatically with age. In addition, there is both diurnal and age-related changes in Histone H3 lysine 9 tri-methylation (H3K9me3) that correlate with the changes in gene expression. Collectively, the data suggest a model where age-related changes in diurnal gene expression occur, in part, due to age-related redistribution of rhythmic facultative heterochromatin. Alterations in heterochromatin appear to be mediated by changes in diurnal lncRNA expression creating an interlocked circadian-chromatin regulatory network that undergoes age-dependent metamorphosis.
2018-01-30 | GSE109855 | GEO
Project description:The circadian rhythm controls timed choreography of gene expression to maintain normal cell physiology and metabolism. The predominant regulatory mechanism of the circadian rhythm is a transcriptional negative feedback loop that facilitates, and is facilitated by, circadian-regulated facultative heterochromatin. The long-term consequence of disrupted diurnal rhythm, or mutations in core clock genes, cause accelerated aging and an increased incidence in age-related diseases. To understand chromatin dynamics underlying age-related changes to circadian transcription, we performed a combined RNA-seq and ChIP-seq at two diurnal time-points for three different age groups. Our analysis focused on uncovering relationships between long non-coding RNA (lncRNA) and age-related changes to heterochromatin. We determined that the core clock genes maintain rhythmic expression regardless of age, but circadian output, including numerous lncRNAs, changes dramatically with age. In addition, there is both diurnal and age-related changes in Histone H3 lysine 9 tri-methylation (H3K9me3) that correlate with the changes in gene expression. Collectively, the data suggest a model where age-related changes in diurnal gene expression occur, in part, due to age-related redistribution of rhythmic facultative heterochromatin. Alterations in heterochromatin appear to be mediated by changes in diurnal lncRNA expression creating an interlocked circadian-chromatin regulatory network that undergoes age-dependent metamorphosis.
2018-01-30 | GSE109854 | GEO
Project description:Animal studies have linked disturbed adipose tissue clock gene rhythms to the pathophysiology of the metabolic syndrome. However, data on molecular clock rhythms in human patients are limited. Therefore, in a standardized real life setting, we compared diurnal gene expression profiles in subcutaneous adipose tissue between obese patients with type 2 diabetes and age-matched healthy lean control subjects, using RNA sequencing. In patients, 1.8% (303 genes) of expressed genes showed significant diurnal rhythms, compared to 8.4% (1421 genes) in healthy controls. In patients, the core clock genes showed reduced amplitude oscillations. Enrichment analysis revealed a loss of rhythm in canonical metabolic pathways including AMPK signaling and cAMP mediated signaling in patients. In conclusion, we provide the first transcriptomics atlas of human adipose tissue diurnal rhythms, and show evidence of decreased diurnal clock and metabolic gene expression rhythms in subcutaneous adipose tissue of obese patients with type 2 diabetes.
2019-01-24 | GSE104674 | GEO
Project description:Kidney physiology has diurnal variation and abnormal circadian rhythm is associated with kidney disease. However, it is not known whether glomeruli, the filtering units in the kidney, are under circadian control. We therefore investigated core circadian clock components in glomeruli, together with their rhythmic targets and modes of regulation.
2024-09-20 | E-MTAB-13457 | biostudies-arrayexpress
Project description:How do transcript levels of leaf-expressed genes change in a normal day-night cycle of the phosphoglucomutase (pgm) mutant? The interest is in genes that are regulated by the circadian clock and the diurnal component (i.e. light, metabolite changes). Plants were grown on soil in a 12/12 h light/dark rhythm at 20°C day and night. 5 weeks after germination the rosettes of the non-flowering plants were harvested, 15 plants per sample. Plants were harvested in series at 6 times every 4 hours, beginning with the end of the night (still in darkness). Experiment Overall Design: A diurnal time series (8 times) was analyzed.
2008-06-12 | E-GEOD-3424 | biostudies-arrayexpress
Project description:The diurnal peak of phagocytosis by the retinal pigment epithelium (RPE) of photoreceptor outer segments is under circadian control, and it is believed that this process involves interactions from both the retina and RPE. Previous studies have demonstrated that a functional circadian clock exists within multiple retinal cell types and RPE cells. Thereby, the aim of the current study was to determine whether the circadian clock in the retina and or RPE controls the diurnal phagocytic peak of photoreceptor outer segments and whether selective disruption of the circadian clock in the RPE would affect RPE cells function and the viability during aging. To that aim, we first generated and validated an RPE tissue-specific KO of the essential clock gene, Bmal1, and then we determined the daily rhythm in phagocytic activity by the RPE in mice lacking a functional circadian clock in the retina or RPE. Then using electroretinography, spectral domain-optical coherence tomography, and optomotor response measurements of visual function we determined the effect of Bmal1 removal in young (6-month-old) and old (18-months old) mice. RPE morphology and lipofuscin accumulation was also determined in young and old mice. Our data show that the circadian clock in the RPE controls the daily diurnal phagocytic peak of POS. Surprisingly, the lack of a functional RPE circadian clock or the diurnal phagocytic peak does not result in any detectable age-related degenerative phenotype in the retina or RPE. Thus, our results demonstrate that the circadian clock in the RPE controls the daily peak in the phagocytic activity. However, the loss of the circadian clock in the RPE does not result in deterioration of photoreceptors or the RPE during aging.
2022-05-12 | GSE191104 | GEO