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

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

PROVIDER: PRJNA751373 | ENA |

REPOSITORIES: ENA

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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

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.

| S-EPMC9575153 | biostudies-literature

Corticosterone induces discrete epigenetic signatures in the dorsal and ventral hippocampus that depend upon sex and genotype: focus on methylated Nr3c1 gene

Project description:It was our goal to discern the genomic signatures of the dorsal and ventral hippocampus, in both mle and female mice after exposure to exogenous corticosterone, an animal model that induces a blunted response to stress. In addition to wildtype mice, we used mice heterozygous for the single nucleotide polymorphism of the gene encoding for brain-derived neurotrophic factor, BDNF Val66Met, a mouse model that shows susceptibility to stress.

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Ventral hippocampal transcriptome analysis after acute corticosterone exposure.

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2022-03-28 | GSE184924 | GEO

Genome-wide identification of glucocorticoid receptor binding sites in the whole hippocampus of adrenalectomised male rats given corticosterone infusion and stressed or non-stressed.

Project description:We have applied next-generation sequencing technology to obtain high through-put profiling of glucocorticoid receptor (GR) DNA binding in whole hippocampus from male rat brain. By obtaining sequence from immunoprecipitated, sonicated chromatin, we have generated genome-wide binding maps for GR in two contexts, testing whether chromatin is primed for GR binding according to the animal's acute experience. In one context (stressed) adrenalectomised rats are infused with corticosterone while undergoing restraint stress. In the second context (non-stressed control) rats are infused with the same corticosterone profile but restraint stress is omitted. We find that GR binding was highly similar suggesting factors other than GR binding may account for any context-dependent alterations in GR function associated with acute stress. We show that GR is positioned near to genes associated with structural and functional organisation of the hippocampus at largely intergenic and intronic sites. Glucocorticoid response element sequences support a majority of GR binding in this tissue but may be reinforced by NF-1 and/or basic-helix loop helix transcription factors binding their nearby recognition motifs. We found little evidence for tethering of GR to other factors, or for the usage of negative glucocorticoid response elements.

2017-02-20 | GSE94008 | GEO

Gene expression changes in mouse hippocampus after overnight exposure to corticosterone

Project description:Gene expression changes in mouse hippocampus after overnight exposure to corticosterone

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Sex differences in neonatal mouse cortex/hippocampus gene expression

Project description:Analysis of mouse genes showing a sex difference in gene expression in the cortex and hippocampus on the day of birth

2014-01-23 | GSE54283 | GEO

Sex differences in neonatal mouse cortex/hippocampus gene expression

Project description:Analysis of mouse genes showing a sex difference in gene expression in the cortex and hippocampus on the day of birth 17 samples, all collected on the afternoon of birth (1pm-3pm local), including 9 male and 8 female samples. All samples include both cortex and hippocampus dissected out from other brain.

2014-01-23 | E-GEOD-54283 | biostudies-arrayexpress

Inflammatory Signatures of Microglia in the Mouse Model of Corticosterone-Induced Depression

Project description:Microglia-mediated inflammation has been recognized as a key feature of major depressive disorder. Although hypercortisolemia is commonly observed in depressed patients and can be predictive of treatment response, how such chronic exposure to this stress hormone may influence microglia is incompletely characterized. Here, we exploited a standard mouse model of depressive-like behaviors induced by repeated peripheral administration of corticosterone. Microglia in the prefrontal cortex of mice were profiled by bulk RNA sequencing, which exhibited increased expression of inflammatory markers. In addition, single-cell RNA sequencing further identified distinct molecular patterns of microglial responses. Moreover, we revealed the up-regulation of Pu.1 and Irf8, the two central transcription factors governing microglia-mediated inflammation, in the prefrontal cortex and hippocampus of corticosterone-treated mice, which similarly occurred in depressed patients' microglia. These results have established the inflammatory signatures of microglia in the mouse model recapitulating hypercortisolemia-related depression, providing new insights into developing diagnostic and therapeutic strategies.

2024-10-01 | GSE274360 | GEO

Corticosterone induces discrete epigenetic signatures in the dorsal and ventral hippocampus that depend upon sex and genotype: focus on methylated Nr3c1 gene

Project description:Corticosterone induces discrete epigenetic signatures in the dorsal and ventral hippocampus that depend upon sex and genotype: focus on methylated Nr3c1 gene

| PRJNA798959 | ENA

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