Hippocampus RNA-sequencing of Q808 against PTZ-induced seizure model
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE193580 | GEO | 2022/03/01
REPOSITORIES: GEO
Similar Datasets
Project description:The present study aimed to use RNA sequencing (RNA-seq) to reveal the gene transcriptomic profile of chronic PTZ-kindled seizure rats and the difference of the PTZ model rat before and after treatment with Q808.
2021-12-01 | GSE189785 | GEO
Project description:Hippocampus RNA-sequencing of Q808 against PTZ-induced seizure model
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Project description:Absence epilepsy syndromes are part of the genetic generalized epilepsies, the pathogenesis of which remains poorly understood, although a polygenic architecture is presumed. Current focus on single molecule or gene identification to elucidate epileptogenic drivers is unable to fully cap-ture the complex dysfunctional interactions occurring at a genetic/proteomic/metabolomic level. Here, we employ a multi-omic, network-based approach to characterize the molecular signature associated with absence epilepsy-like phenotype seen in a well validated rat model of genetic generalized epilepsy with absence seizures. Electroencephalographic and behavioral data was collected from Genetic Absence Epilepsy Rats from Strasbourg (GAERS, n=6) and non-epileptic controls (NEC, n=6), followed by proteomic and metabolomic profiling of the cortical and tha-lamic tissue of rats from both groups. The general framework of weighted correlation network analysis was used to identify groups of highly correlated proteins and metabolites, which were then functionally annotated through joint pathway enrichment analysis. In both brain regions a large protein-metabolite module was found to be highly associated with the GAERS strain, ab-sence seizures and associated anxiety and depressive-like phenotype. Quantitative pathway analysis indicated enrichment in oxidative pathways and a downregulation of the lysine degra-dation pathway in both brain regions. GSTM1 and ALDH2 were identified as central regulatory hubs of the seizure-associated module in the somatosensory cortex and thalamus, respectively. These enzymes are involved in lysine degradation and play important roles in maintaining oxi-dative balance. We conclude that the dysregulated pathways identified in the seizure-associated module may be involved in the aetiology and maintenance of absence seizure activity. This dysregulated activity could potentially be modulated by targeting one or both central regulatory hubs.
2022-08-11 | PXD033987 | Pride
Project description:Transcranial Electrical Stimulation has therapeutic effects on different diseases, including epilepsy. Particularly, Transcranial Focal Stimulation (TFS) has anticonvulsive and antiepileptogenic effects. Nevertheless, the mechanisms and therapeutic targets that induced these effects remain ellusive. We aimed to screen the genetic expression in the cerebral cortex and the hippocampus of rats after a single seizure and TFS to identify potential targets.
2024-03-30 | GSE199183 | GEO
Project description:Seizures that occur during early development are associated with adverse neurodevelopmental outcomes. Causation and mechanisms are currently under investigation. Induction of an early life seizure by kainic acid (KA) in immature rats on post-natal day (P) 7 results in behavioral changes in the adult rat that reflect social and intellectual deficits without overt cellular damage. Our previous work also demonstrated increased expression of CA1 hippocampal long-term potentiation (LTP) and reduced desensitization of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type ionotropic glutamate receptors (AMPA-R) one week following a kainic acid induced seizure (KA-ELS). Here we used RNA sequencing (RNAseq) of mRNA from dorsal hippocampal CA1 to probe changes in mRNA levels one week following KA-ELS as a means to investigate the mechanisms for these functional changes. Ingenuity pathway analysis (IPA) confirmed our previous results by predicting an up-regulation of the synaptic LTP pathway. Differential gene expression results revealed significant differences in 7 gene isoforms. Additional assessments included AMPA-R splice variants and adenosine deaminase acting on RNA 2 (ADAR2) editing sites as a means to determine the mechanism for reduced AMPA-R desensitization. Splice variant analysis demonstrated that KA-ELS result in a small, but significant decrease in the "flop" isoform of Gria3, and editing site analysis revealed significant changes in the editing of a kainate receptor subunit, Grik2, and a serotonin receptor, Htr2c. While these specific changes may not account for altered AMPA-R desensitization, the differences indicate that KA-ELS alters gene expression in the hippocampal CA1 one week after the insult.
2020-04-17 | GSE136913 | GEO
Project description:RNA sequencing analysis of the hippocampus reveals transcriptomic signatures of PTZ-kindled seizure rats and upon treatment of novel anti-convulsant chemical Q808
| PRJNA784521 | ENA
Project description:Microarray profiling was used to investigate gene expression in the hypoxic seizure model of acquired epilepsy in the rat, with the aim of characterizing functional pathways which are persistently activated or repressed during epileptogenesis. Hippocampal and cortical tissues were transcriptionally profiled over a one week period following an initial series of seizures induced by mild hypoxia at post-natal day 10 (P10), and the gene expression data was then analyzed with a focus on gene set enrichment analysis, an approach which emphasizes regulation of entire pathways rather than of individual genes. Animals were subjected to one of three conditions, control condition with no exposure to hypoxia, hypoxic seizures, and hypoxic seizures followed by treatment with the AMPAR antagonist NBQX, a compound tentatively proposed to be a modulator of epileptogenesis. Gene expression in the control samples was found to be consistent with known processes of neuronal maturation in the rat for the given time window. The hypoxic seizure response was found to be saliently enriched for components of the PI3K/mTOR and Wnt signaling pathways, alongside gene sets representative of glutamatergic, synaptic and axonal processes, perhaps regulated as a downstream consequence of activation of these pathways. Wnt signaling components were also found enriched in the more specifically epileptogenic NBQX-responsive gene set. While activation of the mTOR pathway is consistent with its known role in epileptogenesis and strengthens the case for mTOR or PI3K pathway inhibitors as potential anti-epileptogenic drugs, investigation of the role of Wnt signaling and the effect of cognate inhibitors offers a parallel avenue of research toward anti-epileptogenic treatment. Cohorts of ten days old (P10) rat pups were subjected to one of three experimental conditions: 1) a control sham treatment inducing no hypoxic seizures (noHS), 2) a treatment under hypoxia inducing hypoxic seizures (HS), in which each animal underwent a 15 minutes passage at 5% O2, and 3) a treatment with hypoxia inducing hypoxic seizures, followed by four intra-peritoneal injections of NBQX over a 48 h period, starting at 30 minutes post-hypoxia (HS+NBQX). Control vehicle injections of DMSO were performed for the animals under the noHS and HS conditions. Time of occurrence and number of seizures for the animals undergoing hypoxia were recorded and analyzed. Times to the first seizure were found to be exponentially distributed, with mean time to first seizure of 114 seconds, and total count of seizures occurring in the 15 minute hypoxic interval was found to be approximately normally distributed, with mean count 10.6 and standard deviation 2.9. For each treatment condition, cohorts of 4 to 6 rat pups were killed at five sampling times spanning 1 hour to 1 week post-hypoxia (1h, 6h, 12h, 48h, 168h post-hypoxia), for a total of 75 animals sacrificed. Whole cortex and hippocampi were extracted from the sacrificed animals and separately profiled on two Affymetrix high-throughput plate microarrays after RNA quality control, resulting in a total of 144 CEL files encapsulating the gene expression data. The 144 CEL files, generated from scans of the individual microarrays on the two 96-well Affymetrix HT Rat Focus Arrays, were processed according to the MAS5 algorithm, resulting for each input CEL file in output of 24,249 probeset-level intensities and corresponding absent/present calls. For each processed scan, two summary statistics, consisting of the total number of present calls on the chip, and the 75th percentile of present call intensities, were then computed. A quality control step was performed by inspecting for outlier scans in the space of these two statistics (no outliers were found). Additional visual inspection of a heat map of clustered profiles identified a potential tissue assignment swap between two samples, which were conservatively eliminated from further analysis. The resulting 142 quality-controlled profiles were then assembled into a single data matrix, and normalized to each other by linear rescaling of all probeset intensities so as to bring the 75th percentile of present call intensities on all chips to a single common value. These processing steps, and most of the subsequent analyses discussed here, were done using the Gecko gene expression analysis platform (Theilhaber et al., 2004). Additional analyses were performed using the R statistical tools framework (R Development Core Team 2008).
2013-03-06 | E-GEOD-44903 | biostudies-arrayexpress
Project description:Transcriptome analysis of CA1 rat hippocampus 1 week after kainate seizure at P7
| PRJNA564028 | ENA
Project description:Microarray profiling was used to investigate gene expression in the hypoxic seizure model of acquired epilepsy in the rat, with the aim of characterizing functional pathways which are persistently activated or repressed during epileptogenesis. Hippocampal and cortical tissues were transcriptionally profiled over a one week period following an initial series of seizures induced by mild hypoxia at post-natal day 10 (P10), and the gene expression data was then analyzed with a focus on gene set enrichment analysis, an approach which emphasizes regulation of entire pathways rather than of individual genes. Animals were subjected to one of three conditions, control condition with no exposure to hypoxia, hypoxic seizures, and hypoxic seizures followed by treatment with the AMPAR antagonist NBQX, a compound tentatively proposed to be a modulator of epileptogenesis. Gene expression in the control samples was found to be consistent with known processes of neuronal maturation in the rat for the given time window. The hypoxic seizure response was found to be saliently enriched for components of the PI3K/mTOR and Wnt signaling pathways, alongside gene sets representative of glutamatergic, synaptic and axonal processes, perhaps regulated as a downstream consequence of activation of these pathways. Wnt signaling components were also found enriched in the more specifically epileptogenic NBQX-responsive gene set. While activation of the mTOR pathway is consistent with its known role in epileptogenesis and strengthens the case for mTOR or PI3K pathway inhibitors as potential anti-epileptogenic drugs, investigation of the role of Wnt signaling and the effect of cognate inhibitors offers a parallel avenue of research toward anti-epileptogenic treatment.
2013-03-06 | GSE44903 | GEO
Project description:Stroke is a prevalent disorder representing the third leading cause of death and major cause of disability. Post-stroke epilepsy (PSE) has been recognized as a common clinical issue after stroke, accounting for 30-40% of the causes of epilepsy among older adults. In this study, we determined GABAA receptor-mediated seizure susceptibility after PT cerebral stroke in aged mice. Young adult mice around 10 weeks of age are widely used in stroke experiments. However, as most strokes are diagnosed in the elderly and PSE has been recognized as a common clinical incidence after stroke, we utilized photothrombosis (PT) model of cerebral ischemia and examined seizure susceptibility and brain injury using combined behavioral (video) and EEG monitoring and histological (MRI) assessments. To investigate GABAA receptor-mediated convulsive/non-convulsive seizures, lower-doses of pentylenetetrazol (PTZ) was injected. PTZ susceptibility in aging mice increased compared to young adults. One month after PT stroke, aged PT stroke mice exhibited severe convulsive seizures (late-onset). These findings exhibited the increase of GABAA receptor-mediated seizures susceptibility in PT stroke aging mice, but not in young adults.
2023-11-27 | GSE241528 | GEO