The hippocampal response to acute corticosterone elevation is altered in a mouse model for Angelman syndrome
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ABSTRACT:
PROVIDER: PRJNA914211 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22827032_1.fastq.gz | Fastqsanger.gz | |||
| SRR22827032_2.fastq.gz | Fastqsanger.gz | |||
| SRR22827033_1.fastq.gz | Fastqsanger.gz | |||
| SRR22827033_2.fastq.gz | Fastqsanger.gz | |||
| SRR22827034_1.fastq.gz | Fastqsanger.gz |
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Project description:Angelman Syndrome (AS) is a severe neurodevelopmental disorder, caused by the neuronal absence of the ubiquitin protein ligase E3A (UBE3A). UBE3A promotes ubiquitin-mediated protein degradation and functions as a transcriptional coregulator of nuclear hormone receptors, including the glucocorticoid receptor (GR). Previous studies showed anxiety-like behavior and hippocampal-dependent memory disturbances in AS mouse models. Hippocampal GR is an important regulator of the stress response and memory formation, and we therefore investigated whether the absence of UBE3A in AS mice disrupted GR signaling in the hippocampus. We first established a strong cortisol-dependent interaction between the GR ligand binding domain and a UBE3A nuclear receptor box in a high-throughput interaction screen. In vivo, we found that UBE3A-deficient AS mice displayed significantly more variation in circulating corticosterone levels throughout the day compared to wildtypes (WT), with low to undetectable levels of corticosterone at the trough of the circadian cycle. Additionally, we observed an enhanced transcriptomic response in the AS hippocampus following acute corticosterone treatment. Surprisingly, chronic corticosterone treatment showed less contrast between AS and WT mice in the hippocampus and liver transcriptomic responses. This suggests that UBE3A limits the acute stimulation of GR signaling, likely as a member of the GR transcriptional complex. Altogether, these data indicate that AS mice are more sensitive to acute glucocorticoid exposure in the brain compared to WT mice. This suggests that stress responsiveness is altered in AS which could lead to anxiety symptoms.
2022-12-23 | GSE221378 | GEO
Project description:Ventral hippocampal transcriptome analysis after acute corticosterone exposure.
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Project description:Background: As a worldwide threat to mental health, depression affects about 322 million people globally. Recently, the role of gut microbiota dysbiosis on the pathogenesis of depression has received widespread attention, but the underlying mechanism remains elusive.Results: Corticosterone (CORT)-treated mice showed depressive-like behaviors, a reduction in hippocampal neurogenesis, and an altered composition of gut microbiota (GM). Fecal microbial transplantation (FMT) from CORT-treated mice transferred depressive-like phenotypes and their dominant GM, especially bifidobacterium and lactobacillus, to the recipients. Fecal metabolic profiling showed that the relative abundances of fecal ceramides were significantly increased in CORT-treated and the recipient mice. Metagenomic sequencing exposed that bifidobacterium and lactobacillus might be responsible for gut ceramides production in CORT-treated mice. We then found that treatment with ceramides via oral gavage was sufficient to recapitulate the depressive-like phenotypes in wild -type mice. Finally, RNA-sequencing data exposed that most of the differentially expressed genes (DEGs) between ceramides-treated mice and the control group were enriched in oxidative phosphorylation (OXPHOS) pathway. Conclusion: We conclude that chronic exposure to CORT leads to an altered GM composition and consequent ceramides production, thus leading to subtle mitochondrial OXPHOS dysfunction in hippocampus, which may contribute to the development of depressive disorders.
2024-04-01 | GSE229237 | GEO
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.
2022-03-28 | GSE184924 | GEO
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
2016-08-11 | E-GEOD-84249 | biostudies-arrayexpress
Project description:Altered hippocampal transcriptome dynamics following sleep deprivation
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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
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.
2016-08-11 | GSE84249 | GEO
Project description:Background: The epididymis has long been of interest owing to its role in promoting the functional maturation of the male germline. More recent evidence has also implicated the epididymis as an important sensory tissue responsible for remodeling of the sperm epigenome, both under physiological conditions and in response to diverse forms of environmental stress. Despite this knowledge, the intricacies of the molecular pathways involved in regulating the adaptation of epididymal tissue to paternal stressors remains to be fully resolved. Objective: The overall objective of this study was to investigate the direct impact of corticosterone challenge on a tractable epididymal epithelial cell line (i.e., mECap18 cells) in terms of driving adaptation of the cellular proteome and phosphoproteome signaling networks. Materials and methods: The newly developed phosphoproteomic platform EasyPhos coupled with sequencing via an Orbitrap Exploris 480 mass spectrometer was applied to survey global changes in the mECap18 cell (phospho)proteome resulting from sub-chronic (10-day) corticosterone challenge.Results: The imposed corticosterone exposure regimen elicited relatively subtle modifications of the global mECap18 proteome [i.e., only 73/4171 (~1.8%) proteins displayed altered abundance]. By contrast, ~15% of the mECap18 phosphoproteome was substantially altered following corticosterone challenge. In-silico analysis of the corresponding parent proteins revealed an activation of pathways linked to DNA damage repair and oxidative stress responses as well as a reciprocal inhibition of pathways associated with organismal death. Corticosterone challenge also induced the phosphorylation of several proteins linked to the biogenesis of microRNAs. Accordingly, orthogonal validation strategies confirmed an increased in DNA damage, which was ameliorated upon selective kinase inhibition, and an altered abundance profile of a subset of microRNAs in corticosterone-treated cells. Conclusions: Together, these data confirm that epididymal epithelial cells are reactive to corticosterone challenge and that their response is tightly coupled to the opposing action of cellular kinases and phosphatases.
2024-04-08 | PXD028789 | Pride