Cerebrospinal fluid microRNAs are potential biomarkers of temporal lobe epilepsy and status epilepticus
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE94108 | GEO | 2017/06/23
SECONDARY ACCESSION(S): PRJNA368918
REPOSITORIES: GEO
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Project description:Transient brain insults including status epilepticus (SE) can initiate a process termed ‘epileptogenesis’ that results in chronic temporal lobe epilepsy (TLE). As a consequence, the entire tri-synaptic circuit of the hippocampus is fundamentally impaired. A key role in epileptogenesis has been attributed to the CA1 region as the last relay station in the hippocampal circuit and as site of aberrant plasticity, e.g. mediated by acquired channelopathies. The transcriptional profiles of the distinct hippocampal neurons are highly dynamic during epileptogenesis. Here, we aimed to elucidate the early SE-elicited mRNA signature changes and the respective upstream regulatory cascades in CA1. RNA sequencing of CA1 was performed in the mouse pilocarpine-induced SE model at multiple time points ranging from 6 to 72 hours after the initial insult. Bioinformatics was used to decipher altered gene expression, signalling cascades and their corresponding cell type profiles. Robust transcriptomic changes were detected at 6h after SE and at subsequent time points during early epileptogenesis. Major differentially expressed mRNAs encoded primarily immediate early and excitability-related gene products, as well as genes encoding immune signalling factors.
2023-12-20 | GSE241219 | GEO
Project description:Temporal lobe epilepsy (TLE) can develop from alterations in hippocampal structure and circuit characteristics, and can be modeled in mice by administration of kainic acid (KA). Adult neurogenesis in the dentate gyrus (DG) contributes to hippocampal functions and has been reported to contribute to the development of TLE. Some of the phenotypical changes include neural stem and precursor cells (NPSC) apoptosis, shortly after their birth, before they produce hippocampal neurons. Here we explored these early phenotypical changes in the DG 3 days after systemic KA administration to mice. Our specific aim was to understand the molecular mechanisms underlying altered apoptosis levels in NSPC following KA-induced status epilepticus (KA-SE). Accordingly, we chose a multi-omics experimental setup and analyzed DG tissue samples using proteomics, transcriptomics and microRNA profiling techniques. We here present a description of how these date were obtained and provide them to others for further analysis and validation. This may help to further identify and characterize molecular mechanisms involved in the alterations induced shortly after KA-SE in the mouse DG. Total RNA obtained from dentate gyrus 72h after mice were subjected to repeated low dose kainic acid induced status epilepticus or saline i.p. injections
2016-03-12 | E-GEOD-79131 | biostudies-arrayexpress
Project description:Temporal lobe epilepsy (TLE) can develop from alterations in hippocampal structure and circuit characteristics, and can be modeled in mice by administration of kainic acid (KA). Adult neurogenesis in the dentate gyrus (DG) contributes to hippocampal functions and has been reported to contribute to the development of TLE. Some of the phenotypical changes include neural stem and precursor cells (NPSC) apoptosis, shortly after their birth, before they produce hippocampal neurons. Here we explored these early phenotypical changes in the DG 3 days after systemic KA administration to mice. Our specific aim was to understand the molecular mechanisms underlying altered apoptosis levels in NSPC following KA-induced status epilepticus (KA-SE). Accordingly, we chose a multi-omics experimental setup and analyzed DG tissue samples using proteomics, transcriptomics and microRNA profiling techniques. We here present a description of how these date were obtained and provide them to others for further analysis and validation. This may help to further identify and characterize molecular mechanisms involved in the alterations induced shortly after KA-SE in the mouse DG. Total RNA obtained from dentate gyrus 72h after mice were subjected to repeated low dose kainic acid induced status epilepticus or saline i.p. injections
2016-03-12 | E-GEOD-79129 | biostudies-arrayexpress
Project description:There are no blood-based molecular biomarkers of temporal lobe epilepsy (TLE) to support clinical diagnosis. MicroRNAs are short noncoding RNAs with strong biomarker potential due to their cell-specific expression, mechanistic links to brain excitability, and stable and reliable detection in biofluids. Altered expression of circulating microRNAs has been reported in human epilepsy, but most studies collected samples from one clinical site, relied on a single platform for profiling or conducted minimal validation. We collected plasma samples from video-electroencephalogram-monitored adult TLE patients at epilepsy specialist centers in two different countries, performed genome-wide PCR-based and RNA sequencing during the discovery phase and validated in a large cohort of samples (>300 samples) that included patients with psychogenic non-epileptic seizures. After profiling, validation of the discovery cohort and validation in the larger patient groups we identified miR-27a-3p, miR-328-3p and miR-654-3p with strong TLE biomarker potential. Plasma levels of these microRNAs were regulated in the same direction in plasma from epileptic mice, and furthermore were not different to healthy controls in patients with psychogenic non-epileptic seizures. The biomarker potential was extended by determining microRNA copy number in plasma and we demonstrate rapid detection of these microRNAs using an electrochemical RNA microfluidic disk as a prototype point-of-care device. Investigation of the molecular transport mechanism in plasma determined analysis of all three microRNAs within the exosome-enriched provided highest diagnostic accuracy while levels of Argonaute-bound miR-328-3p selectively increased in patient samples collected after seizures. In situ hybridization revealed the presence of miR-27a-3p and miR-328-3p within neurons in human brain and bioinformatics analysis predicted targets linked to growth factor signaling and apoptosis. Taken together, this study extends evidence for the biomarker potential of circulating microRNAs for epilepsy diagnosis and mechanistic links to underlying pathomechanisms. microRNA expression in the plasma of 16 patients with TLE, before and after seizure, and 16 controls was measured by TaqMan OpenArray Human MicroRNA Panel.
2019-01-02 | GSE114700 | GEO
Project description:There are no blood-based molecular biomarkers of temporal lobe epilepsy (TLE) to support clinical diagnosis. MicroRNAs are short noncoding RNAs with strong biomarker potential due to their cell-specific expression, mechanistic links to brain excitability, and stable and reliable detection in biofluids. Altered expression of circulating microRNAs has been reported in human epilepsy, but most studies collected samples from one clinical site, relied on a single platform for profiling or conducted minimal validation. We collected plasma samples from video-electroencephalogram-monitored adult TLE patients at epilepsy specialist centers in two different countries, performed genome-wide PCR-based and RNA sequencing during the discovery phase and validated in a large cohort of samples (>300 samples) that included patients with psychogenic non-epileptic seizures. After profiling, validation of the discovery cohort and validation in the larger patient groups we identified miR-27a-3p, miR-328-3p and miR-654-3p with strong TLE biomarker potential. Plasma levels of these microRNAs were regulated in the same direction in plasma from epileptic mice, and furthermore were not different to healthy controls in patients with psychogenic non-epileptic seizures. The biomarker potential was extended by determining microRNA copy number in plasma and we demonstrate rapid detection of these microRNAs using an electrochemical RNA microfluidic disk as a prototype point-of-care device. Investigation of the molecular transport mechanism in plasma determined analysis of all three microRNAs within the exosome-enriched provided highest diagnostic accuracy while levels of Argonaute-bound miR-328-3p selectively increased in patient samples collected after seizures. In situ hybridization revealed the presence of miR-27a-3p and miR-328-3p within neurons in human brain and bioinformatics analysis predicted targets linked to growth factor signaling and apoptosis. Taken together, this study extends evidence for the biomarker potential of circulating microRNAs for epilepsy diagnosis and mechanistic links to underlying pathomechanisms. microRNA expression in the plasma of 16 patients with TLE, before and after seizure, and 16 controls was measured by TaqMan OpenArray Human MicroRNA Panel.
2019-01-02 | GSE114697 | GEO
Project description:Temporal lobe epilepsy (TLE) can develop from alterations in hippocampal structure and circuit characteristics, and can be modeled in mice by administration of kainic acid (KA). Adult neurogenesis in the dentate gyrus (DG) contributes to hippocampal functions and has been reported to contribute to the development of TLE. Some of the phenotypical changes include neural stem and precursor cells (NPSC) apoptosis, shortly after their birth, before they produce hippocampal neurons. Here we explored these early phenotypical changes in the DG 3 days after systemic KA administration to mice. Our specific aim was to understand the molecular mechanisms underlying altered apoptosis levels in NSPC following KA-induced status epilepticus (KA-SE). Accordingly, we chose a multi-omics experimental setup and analyzed DG tissue samples using proteomics, transcriptomics and microRNA profiling techniques. We here present a description of how these date were obtained and provide them to others for further analysis and validation. This may help to further identify and characterize molecular mechanisms involved in the alterations induced shortly after KA-SE in the mouse DG.
2016-03-12 | GSE79131 | GEO
Project description:Temporal lobe epilepsy (TLE) can develop from alterations in hippocampal structure and circuit characteristics, and can be modeled in mice by administration of kainic acid (KA). Adult neurogenesis in the dentate gyrus (DG) contributes to hippocampal functions and has been reported to contribute to the development of TLE. Some of the phenotypical changes include neural stem and precursor cells (NPSC) apoptosis, shortly after their birth, before they produce hippocampal neurons. Here we explored these early phenotypical changes in the DG 3 days after systemic KA administration to mice. Our specific aim was to understand the molecular mechanisms underlying altered apoptosis levels in NSPC following KA-induced status epilepticus (KA-SE). Accordingly, we chose a multi-omics experimental setup and analyzed DG tissue samples using proteomics, transcriptomics and microRNA profiling techniques. We here present a description of how these date were obtained and provide them to others for further analysis and validation. This may help to further identify and characterize molecular mechanisms involved in the alterations induced shortly after KA-SE in the mouse DG.
2016-03-12 | GSE79129 | GEO
Project description:Status epilepticus (SE) is a life-threatening condition that can give rise to a number of neurological disorders, including learning deficits, depression, and epilepsy. Many of the effects of SE appear to be mediated by alterations in gene expression. To gain deeper insight into how SE affects the transcriptome, we employed the pilocarpine SE model in mice and Illumina-based high-throughput sequencing to characterize alterations in gene expression from the induction of SE, to the development of spontaneous seizure activity. While some genes were upregulated over the entire course of the pathological progression, each of the three sequenced time points (12-hour, 10-days and 6-weeks post-SE) had a largely unique transcriptional profile. Hence, genes that regulate synaptic physiology and transcription were most prominently altered at 12-hours post-SE; at 10-days post-SE, marked changes in metabolic and homeostatic gene expression were detected; at 6-weeks, substantial changes in the expression of cell excitability and morphogenesis genes were detected. At the level of cell signaling, KEGG analysis revealed dynamic changes within the MAPK pathways, as well as in CREB-associated gene expression. Notably, the inducible expression of several noncoding transcripts was also detected. These findings offer potential new insights into the cellular events that shape SE-evoked pathology.
2015-08-27 | GSE72402 | GEO
Project description:Temporal lobe epilepsy (TLE) is the most frequent type of focal epilepsy in adults, typically resistant to pharmacological treatment and mostly present with cognitive impairment and psychiatric comorbidities. The most common neuropathological hallmark in TLE patients is hippocampal sclerosis(HS). However, the underlying molecular mechanisms involved remain poorly characterized. Dentate gyrus(DG), one specific hippocampal subarea, structural and functional changes imply a key involvement of the DG in the development of TLE. In this study, isobaric tags for relative and absolute quantitation (iTRAQ) -based quantitative proteomic technique was performed to analysis of hippocampal DG obtained from patients with TLE-HS compared to control samples obtained from the autopsy. Our proteomic data identified 5583 proteins, of which 82 proteins were up-regulated and 90 proteins were down-regulated. Bioinformatics analysis indicated that differential expressed proteins enriched in “synaptic vesicle”, “mitochondrion”, “cell-cell adhesion”, “regulation of synaptic plasticity”, “ATP binding” and “Oxidative phosphorylation”. Protein-protein interaction network analysis found a pivotal module of 10 proteins that relate to “Oxidative phosphorylation”. This study is the first to investigate proteomic alterations in DG region of TLE-HS patients, and pave the way to better understanding of epileptogenesis mechanisms and future therapeutic intervention.
2021-01-18 | PXD023048 | Pride
Project description:MicroRNAs (miRNAs) have been found to participate in the pathogenesis of several neurological diseases including epilepsy. To date, the expression and functions of miRNAs in chronic temporal lobe epilepsy (TLE), the most common type of refractory epilepsy in adults, have not been well characterized. Here, we adopted high-throughput sequencing to investigate miRNA expression profile in a chronic TLE model induced by amygdala stimulation
2017-02-09 | GSE52443 | GEO