Similar Datasets
Project description:These data describe single-cell RNA sequencing in cerebral organoids treated with the glucocorticoid Dexamethasone or with a vehicle control (DMSO) at 90 days in culture.
2021-12-02 | GSE189534 | GEO
Project description:These data describe single-cell RNA sequencing in cerebral organoids treated with the glucocorticoid Dexamethasone or with a vehicle control (DMSO) at different culture time-points (Day-30, Day-60 and Day-90).
2021-12-02 | GSE189533 | GEO
Project description:Cell-Type-Specific Impact of Glucocorticoid Receptor Activation on the Developing Brain: A Cerebral Organoid Study
| PRJNA783333 | ENA
Project description:Cell-Type-Specific Impact of Glucocorticoid Receptor Activation on the Developing Brain: A Cerebral Organoid Study [Wafergen iCell8]
| PRJNA783339 | ENA
Project description:Cell-Type-Specific Impact of Glucocorticoid Receptor Activation on the Developing Brain: A Cerebral Organoid Study [10x Genomics]
| PRJNA783338 | ENA
Project description:ObjectiveGlucocorticoid levels rise rapidly following status epilepticus and remain elevated for weeks after the injury. To determine whether glucocorticoid receptor activation contributes to the pathological sequelae of status epilepticus, mice were treated with a novel glucocorticoid receptor modulator, C108297.MethodsMice were treated with either C108297 or vehicle for 10 days beginning one day after pilocarpine-induced status epilepticus. Baseline and stress-induced glucocorticoid secretion were assessed to determine whether hypothalamic-pituitary-adrenal axis hyperreactivity could be controlled. Status epilepticus-induced pathology was assessed by quantifying ectopic hippocampal granule cell density, microglial density, astrocyte density and mossy cell loss. Neuronal network function was examined indirectly by determining the density of Fos immunoreactive neurons following restraint stress.ResultsTreatment with C108297 attenuated corticosterone hypersecretion after status epilepticus. Treatment also decreased the density of hilar ectopic granule cells and reduced microglial proliferation. Mossy cell loss, on the other hand, was not prevented in treated mice. C108297 altered the cellular distribution of Fos protein but did not restore the normal pattern of expression.InterpretationResults demonstrate that baseline corticosterone levels can be normalized with C108297, and implicate glucocorticoid signaling in the development of structural changes following status epilepticus. These findings support the further development of glucocorticoid receptor modulators as novel therapeutics for the prevention of brain pathology following status epilepticus.
| S-EPMC8169587 | biostudies-literature
Project description:Cortisol is the primary corticosteroid in teleosts that is released in response to stressor activation of the hypothalamus-pituitary-interrenal axis. The target tissue action of this hormone is primarily mediated by the intracellular glucocorticoid receptor (GR), a ligand-bound transcription factor. In developing zebrafish (Danio rerio) embryos, GR transcripts and cortisol are maternally deposited into the oocyte prior to fertilization and influence early embryogenesis. To better understand of the molecular mechanisms involved, we investigated changes in the developmental transcriptome prior to hatch, in response to morpholino oligonucleotide knockdown of GR using the Agilent zebrafish microarray platform. A total of 1313 and 836 mRNA transcripts were significantly changed at 24 and 36 hours post fertilization (hpf), respectively. Functional analysis revealed numerous developmental processes under GR regulation, including neurogenesis, eye development, skeletal and cardiac muscle formation. Together, this study underscores a critical role for glucocorticoid signaling in programming molecular events essential for zebrafish development.
| S-EPMC3858477 | biostudies-literature
Project description:Disrupted cerebellar development and injury is associated with impairments in both motor and non-motor domains. Methods to non-invasively characterize cerebellar afferent and efferent connections during early development are lacking. The aim of this study was to assess the feasibility of delineating cortico-ponto-cerebellar (CPC) and cerebello-thalamo-cortical (CTC) white matter tracts during brain development using high angular resolution diffusion imaging (HARDI). HARDI data were obtained in 24 infants born between 24+6 and 39 weeks gestational age (median 33+4 weeks) and scanned between 29+1 and 44 weeks postmenstrual age (PMA) (median 37+1 weeks). Probabilistic tractography of CPC and CTC fibers was performed using constrained spherical deconvolution. Connections between cerebellum and contralateral cerebral hemisphere were identified in all infants studied. Fractional anisotropy (FA) values of CTC and CPC pathways increased with increasing PMA at scan (p < 0.001). The supratentorial regions connecting to contralateral cerebellum in most subjects, irrespective of PMA at scan, included the precentral cortex, superior frontal cortex, supplementary motor area, insula, postcentral cortex, precuneus, and paracentral lobule. This study demonstrates the feasibility of assessing CTC and CPC white matter connectivity in vivo during the early stages of development. The ability to assess cerebellar connectivity during this critical developmental period may help improve our understanding of the role of the cerebellum in a wide range of neuromotor and neurocognitive disorders.
| S-EPMC5406415 | biostudies-literature
Project description:The molecular basis underlying the physiologically well-defined orexigenic function of glucocorticoid (Gc) is unclear. Brain-specific homeobox factor (Bsx) is a positive regulator of the orexigenic neuropeptide, agouti-related peptide (AgRP), in AgRP neurons of the hypothalamic arcuate nucleus. Here, we show that in response to fasting-elevated Gc levels, Gc receptor (GR) and Bsx synergize to direct activation of AgRP transcription. This synergy is dictated by unique sequence features in a novel Gc response element in AgRP (AgRP-GRE). In contrast to AgRP-GRE, Bsx suppresses transactivation directed by many conventional GREs, functioning as a gene context-dependent modulator of GR actions or a target selector for GR. Consistent with this finding, AgRP-GRE drives fasting-dependent activation of a target gene specifically in GR(+) Bsx(+) AgRP neurons. These results define AgRP as a common orexigenic target gene of GR and Bsx and provide an opportunity to identify their additional common targets, facilitating our understanding of the molecular basis underlying the orexigenic activity of Gc and Bsx.
| S-EPMC3700135 | biostudies-literature
Project description:Background and aimGlucocorticoids are the only first-line drugs for severe alcoholic hepatitis (AH), with limited efficacy and various side effects on extrahepatic tissues. Liver-targeting glucocorticoid therapy may have multiple advantages over systemic glucocorticoid for AH. The aim of this study was to determine the role of hepatocellular glucocorticoid receptor (GR) in alcohol-associated steatosis (AS) and AH.Materials and methodsAS was induced by a high-fat diet plus binge alcohol in adult male and female mice with liver-specific knockout (LKO) and heterozygote of GR. AH was induced by chronic-plus-binge in middle-aged male mice with liver-specific knockin of GR. Changes in hepatic mRNA and protein expression were determined by quantitative real-time polymerase chain reaction and Western blot.ResultsGR-LKO aggravated steatosis and decreased hepatic expression and circulating levels of albumin in both genders of AS mice but only increased markers of liver injury in male AS mice. Marked steatosis in GR-LKO mice was associated with induction of lipogenic genes and down-regulation of bile acid synthetic genes. Hepatic protein levels of GR, hepatocyte nuclear factor 4 alpha, and phosphorylated signal transducer and activator of transcription 3 were gene-dosage-dependently decreased, whereas that of lipogenic ATP citrate lyase was increased in male GR heterozygote and LKO mice. Interestingly, hepatic expression of estrogen receptor alpha (ERα) was induced, and the essential estrogen-inactivating enzyme sulfotransferase 1e1 was gene-dosage-dependently down-regulated in GR heterozygote and knockout AS mice, which was associated with induction of ERα-target genes. Liver-specific knockin of GR protected against liver injury and steatohepatitis in middle-aged AH mice.ConclusionsHepatic GR deficiency plays a crucial role in the pathogenesis of AS induced by high-fat diet plus binge, and liver-specific overexpression/activation of GR protects against chronic-plus-binge-induced AH in middle-aged mice. Hepatocellular GR is important for protection against AS and AH.
| S-EPMC11771271 | biostudies-literature