P2X7 receptor-dependent microRNA expression profile in the brain following status epilepticus in mice
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PROVIDER: PRJNA641719 | ENA |
REPOSITORIES: ENA
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Project description:We explored the microRNA expression profile in mice lacking the P2X7 receptor before and after seizures. Genome-wide microRNA profiling was performed using hippocampi from wild-type and P2X7 knock-out mice following status epilepticus induced by intraamygdala kainic acid. This revealed that genetic deletion of the P2X7 receptor results in distinct patterns of microRNA expression. Specifically, we found that in vehicle-injected control mice the lack of P2X7 resulted in the up-regulation of 50 microRNAs and down-regulation of 35 microRNAs. Post-status epilepticus, P2X7 deficiency let to the up-regulation of 44 microRNAs while 13 microRNAs were down-regulated. Moreover, there was only limited overlap between identified P2X7-dependent microRNAs between control conditions and post-status epilepticus, suggesting P2X7 regulating the expression of different microRNAs during normal physiology and pathology. Bioinformatics analysis found that genes targeted via P2X7-dependent microRNAs were particularly overrepresented within pathways involved in intracellular signalling, inflammation and cell death, processes repeatedly linked to P2X7. Moreover, whereas genes involved in signalling pathways and inflammation were common among up-and down-regulated P2X7-dependent miRNAs during physiological and pathological conditions, genes associated with cell death seemed to be restricted to up-regulated miRNAs during both physiological conditions and post-status epilepticus. Taken together, our results demonstrate that P2X7 impacts on the expression profile of microRNAs in the brain, thereby possibly contributing to both the maintenance of normal cellular homeostasis and pathological processes.
2020-06-25 | GSE153204 | GEO
Project description:Here, we characterised the effects of experimental status epilepticus on the expression of exosome biosynthesis components and analysed microRNA content in exosome-enriched fractions prepared from the mouse hippocampus. Status epilepticus induced by unilateral intra-amygdala kainic acid resulted in acute subfield-specific, bi-directional changes in transcripts associated with exosome biosynthesis including up-regulation of ESCRT–dependent and –independent pathways. Increased expression of exosome components including Alix were detectable in samples obtained two weeks after status epilepticus and changes occurred in both the ipsilateral and contralateral hippocampus. Small RNAseq analysis of exosome-enriched fractions prepared using two different techniques detected a rich diversity of conserved microRNAs and determined status epilepticus selectively alters microRNA contents, including upregulation of the glia-enriched miR-21a-3p. We also characterized editing sites of the exosome-enriched miRNAs and found six exosome-enriched miRNAs that were Adenosine-to-Inosine (ADAR) edited with the majority of the editing events predicted to occur within miRNA seed regions. However, the prevalence of these editing events was not altered by status epilepticus. These studies demonstrate status epilepticus alters the exosome pathway and its microRNA content, but not editing patterns.
2019-12-12 | GSE136695 | GEO
Project description:Altered Biogenesis and MicroRNA Content of Hippocampal Exosomes Following Experimental Status Epilepticus
| PRJNA563073 | ENA
Project description:MicroRNAs (miRNAs) are small and endogenously expressed non-coding RNAs that negatively regulate the expression of protein-coding genes at the translational level. Emerging evidence suggests that miRNAs play critical roles in central nervous system under physiological and pathological conditions. However, their expression and functions in status epilepticus (SE) have not been well characterized thus far. Here, we characterized miRNA expression profile in rat hippocampus at 24 hours following SE induced by amygdala stimulation.
2014-01-06 | GSE50940 | GEO
Project description:The ionotropic ATP-gated P2X7 receptor is an important contributor to inflammatory signaling cascades via the release of Interleukin-1β, as well as having roles in cell death, neuronal plasticity and the release of neurotransmitters. Accordingly, there is interest in targeting the P2X7 receptor for the treatment of epilepsy. However, the signaling pathways downstream of P2X7 receptor activation remain incompletely understood. Notably, recent studies showed that P2X7 receptor expression is controlled, in part, by microRNAs (miRNAs). Here, we explored P2X7 receptor-dependent microRNA expression by comparing microRNA expression profiles of wild-type (wt) and P2X7 receptor knockout mice before and after status epilepticus. Genome-wide microRNA profiling was performed using hippocampi from wt and P2X7 receptor knockout mice following status epilepticus induced by intra-amygdala kainic acid. This revealed that the genetic deletion of the P2X7 receptor results in distinct patterns of microRNA expression. Specifically, we found that in vehicle-injected control mice, the lack of the P2X7 receptor resulted in the up-regulation of 50 microRNAs and down-regulation of 35 microRNAs. Post-status epilepticus, P2X7 receptor deficiency led to the up-regulation of 44 microRNAs while 13 microRNAs were down-regulated. Moreover, there was only limited overlap among identified P2X7 receptor-dependent microRNAs between control conditions and post-status epilepticus, suggesting that the P2X7 receptor regulates the expression of different microRNAs during normal physiology and pathology. Bioinformatic analysis revealed that genes targeted by P2X7 receptor-dependent microRNAs were particularly overrepresented in pathways involved in intracellular signaling, inflammation, and cell death; processes that have been repeatedly associated with P2X7 receptor activation. Moreover, whereas genes involved in signaling pathways and inflammation were common among up- and down-regulated P2X7 receptor-dependent microRNAs during physiological and pathological conditions, genes associated with cell death seemed to be restricted to up-regulated microRNAs during both physiological conditions and post-status epilepticus. Taken together, our results demonstrate that the P2X7 receptor impacts on the expression profile of microRNAs in the brain, thereby possibly contributing to both the maintenance of normal cellular homeostasis and pathological processes.
| S-EPMC7485385 | biostudies-literature
Project description:The aim of this work was to identify mRNA expression changes in the ipsilateral hippocampus in the intraamygdala kainic acid (KA) mouse model of status epilepticus. In this model, status epilepticus (prolonged damaging seizures) are triggered by an intraamygdala KA injection. All mice develop epilepsy after a short latency period of 3-5 days. For our experiments, 10-week old mice with a C57BL/6 background were either injected with intraamygdala KA (n = 18) or vehicle (PBS, n = 18). Mice were sacrificed 8 hours following status epilepticus (acute pathology) or 14 days post-status epilepticus (timepoint at which all mice suffer from chronic epilepsy) and ipsilateral hippocampi were quickly dissected and pooled into 3 groups (n = 3 per pooled sample).
2021-09-09 | GSE122228 | GEO
Project description:Mice lacking miR-22 displayed normal behavior and brain structure and developed similar status epilepticus after intraamygdala kainic acid compared to wildtype animals. Subsequent continuous EEG monitoring revealed an accelerated and exacerbated epileptogenesis whereby spontaneous seizures began sooner, occurred more frequently and were of longer duration in miR-22-deficient mice. RNA sequencing analysis of the hippocampus of mice during the period of epileptogenesis revealed a widespread suppression of inflammatory signalling in the hippocampus of miR-22-deficient mice. Taken together, these findings indicate a role for miR-22 in establishing early inflammatory responses to status epilepticus. Inflammatory signalling may serve anti-epileptogenic functions and cautions the timing of anti-inflammatory treatments for the treatment of status epilepticus.
2020-06-24 | GSE147466 | GEO
Project description:Estrogen protects neurotransmission transcriptome during status epilepticus
| PRJNA421197 | ENA
Project description:Highly dynamic inflammatory and excitability transcriptional profiles in hippocampal CA1 following status epilepticus
| PRJNA1006742 | ENA
Project description:MicroRNAs (miRNAs) are small and endogenously expressed non-coding RNAs that negatively regulate the expression of protein-coding genes at the translational level. Emerging evidence suggests that miRNAs play critical roles in central nervous system under physiological and pathological conditions. However, their expression and functions in status epilepticus (SE) have not been well characterized thus far. Here, we characterized miRNA expression profile in rat hippocampus at 24 hours following SE induced by amygdala stimulation. Hippocampus miRNA profiles of experimental group and control group were generated by deep sequencing, using Hiseq 2000.
2014-01-06 | E-GEOD-50940 | biostudies-arrayexpress