Estrogen protects neurotransmission transcriptome during status epilepticus
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PROVIDER: PRJNA421197 | ENA |
REPOSITORIES: ENA
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Project description:Epilepsy in women is often accompanied by hormonal disturbances including irregular cycles and premature onset of menopause. Decline in estrogen levels results in increased risk for neurodegenerative diseases, with strong participation of chronic inflammation. We have shown that estradiol (EB) has neuroprotective effects against seizure-induced damage in the sensitive hilar region of hippocampal dentate gyrus associated with neuropeptide Y (NPY) upregulation. Here, we quantify the alterations caused by kainic acid-induced status epilepticus in the glutamatergic, GABAergic, dopaminergic, cholinergic and serotonergic synapse transcriptomes of dentate gyrus of ovariectomized female rats and the recovery effects of the EB replacement. Our data indicate that the EB replacement reduces the number of significantly regulated genes in seizured ovariectomized female rats by about 45%. The new measure Pathway Restoration Efficiency (PRE) indicates the dopaminergic synapse to be the most protected (65%) and the GABAergic synapse the least protected (37%) by the EB replacement.
2017-12-06 | GSE107725 | GEO
Project description:Women with epilepsy commonly have premature onset of menopause. The decrease in estrogen levels is associated with increased occurrence of neurodegenerative processes and cognitive decline. Previously, we found that estradiol (E2) replacement in ovariectomized (OVX) female rats significantly reduced the seizure-related damage in the sensitive hilar region of hippocampal dentate gyrus (DG). However, the complex mechanisms by which E2 empowers the genomic fabrics of neurotransmission to resist damaging effects of status epilepticus (SE) are still unclear. We determined the protective effects of the estradiol replacement against kainic acid-induced SE-associated transcriptomic alterations in the DG of OVX rats. Without E2 replacement, SE altered expression of 44% of the DG genes. SE affected all major functional pathways, including apoptosis (61%), Alzheimer's disease (47%), cell cycle (59%), long-term potentiation (62%), and depression (55%), as well as synaptic vesicle cycle (62%), glutamatergic (53%), GABAergic (49%), cholinergic (52%), dopaminergic (55%), and serotonergic (49%) neurotransmission. However, in rats with E2 replacement the percentage of significantly affected genes after SE was reduced to the average 11% (from 8% for apoptosis to 32% for GABAergic synapse). Interestingly, while SE down-regulated most of the synaptic receptor genes in oil-injected females it had little effect on these receptors after E2-replacement. Our novel Pathway Protection analysis indicated that the E2-replacement prevented SE-related damage from 50% for GABA to 75% for dopaminergic transmission. The 15% synergistic expression between genes involved in estrogen signaling (ESG) and neurotransmission explains why low E2 levels result in down-regulation of neurotransmission. Interestingly, in animals with E2-replacement, SE switched 131 synergistically expressed ESG-neurotransmission gene pairs into antagonistically expressed gene pairs. Thus, the ESG pathway acts like a buffer against SE-induced alteration of neurotransmission that may contribute to the E2-mediated maintenance of brain function after the SE injury in postmenopausal women. We also show that the long-term potentiation is lost in OVX rats following SE but not in those with E2 replacement. The electrophysiological findings in OVX female rats with SE are corroborated by the high percentage of long-term potentiation regulated genes (62%) in oil-injected while only 13% of genes were regulated following SE in E2-replaced rats.
| S-EPMC6019481 | biostudies-literature
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:miRNA array comparing the transcription profile of control rats and rats after intra-hippocampal pilocarpine-induced Status Epilepticus (PILO-SE).
2016-04-28 | E-MTAB-4633 | biostudies-arrayexpress
Project description:Comparison of methylation profiles in the CA3 region of the mouse hippocampus in epileptic tolerance and status epilepticus.
2012-02-09 | E-MEXP-3503 | biostudies-arrayexpress
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: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:Status Epilepticus (SE) is an abnormally prolonged seizure that results from either a failure of mechanisms that terminate seizures or from initiating mechanisms that inherently lead to prolonged seizures. Here we report an unbiased analysis of the hippocampal transcriptome of mice with targeted disruption of Dio2 in the astrocytes (Astro-D2KO mouse) undergoing 3 h SE.
2018-05-25 | GSE114887 | GEO
Project description:The phosphorylation-based signalling and protein changes occurring in the early phases after a pathophysiological insult, like status epilepticus, have not been detailed. To this end, the hippocampi of mice treated with pilocarpine and diazepam were examined by mass spectrometry at 4 and 24 h post-status epilepticus at vast depth using the tandem mass tag 11-plex system. In the accompanying article, the results implicated posttranscriptional regulatory proteins as early targets of increased phosphorylation. Also, the major targets of decreased phosphorylation at 4 h and 24 h were a subset of post synaptic density scaffold proteins, ion channels and neurotransmitter receptors. Many proteins targeted by dephosphorylation at 4 h also had decreased protein abundance at 24 h, indicating a phosphatase-mediated weakening of synapses.
2024-02-22 | PXD038241 | Pride