Gene expression profiles of hippocampal astrocytes in mesial temporal lobe epilepsy model mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE237321 | GEO | 2025/12/04
REPOSITORIES: GEO
Dataset's files
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| GSE237321_RAW.tar | Raw | |||
| GSE237321_counts_all_samples.xlsx | Xlsx | |||
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Project description:The epilepsies represent one of the most common neurological disorders. Mesial temporal lobe epilepsies (MTLE) are the most frequent form of partial epilepsies and display frequent resistance to anti-epileptic drugs thus representing a major health care problem. In TLE, the origin of seizure activity typically involves the hippocampal formation, which displays major neuropathological features, described with the term hippocampal sclerosis (HS). HS is the most frequent pathological substrate of refractory mesial temporal lobe epilepsy. Complex partial seizures (CPS) are the predominant seizure type associated with medial temporal lobe epilepsy. MTLE is commonly due to mesial temporal sclerosis (MTS). The biology underlying the epilepstic seizures and the transcriptome associated to the seizure in intractable medial temporal lobe epilepsy is ill understood. The aim of the study was to identify potential biomarkers that could identify epileptic seizure. Thus we performed transcriptome profiling of ten medial temporal lobe epilepsy cases which are resistant to the drug and underwent temporal lobectomy. The cases constitutes of patients with intractable complex partial seizure, treated medically and have undergone detailed presurgical evaluation and subjected to surgery for standard temporal lobectomy and amygdalo-hippocampectomy. The spiking areas identified after the electrocorticography will form the test tissues, which compared with the nonspiking areas removed during the surgery, from the same patient. This could probably form one of the appropriate controls, as test and control are from same patient, which eliminates the genome variations that could incur due to the comparison with the tissues from the another patient. Also this could get rid of expression changes due to the treatments undergone by the patient. We performed two color microarray wherein we labled seizure focus (spiking area) with Cy5 and non-seizure region tissues (non-spiking) with Cy3. As a strategy to test the possibility of potential diagnostic biomarkers we are intended to test the differentially regulated molecules in an independent set of epilepsy samples. Two color experiment
2012-12-01 | E-GEOD-25453 | biostudies-arrayexpress
Project description:The epilepsies represent one of the most common neurological disorders. Mesial temporal lobe epilepsies (MTLE) are the most frequent form of partial epilepsies and display frequent resistance to anti-epileptic drugs thus representing a major health care problem. In TLE, the origin of seizure activity typically involves the hippocampal formation, which displays major neuropathological features, described with the term hippocampal sclerosis (HS). HS is the most frequent pathological substrate of refractory mesial temporal lobe epilepsy. Complex partial seizures (CPS) are the predominant seizure type associated with medial temporal lobe epilepsy. MTLE is commonly due to mesial temporal sclerosis (MTS). The biology underlying the epilepstic seizures and the transcriptome associated to the seizure in intractable medial temporal lobe epilepsy is ill understood. The aim of the study was to identify potential biomarkers that could identify epileptic seizure. Thus we performed transcriptome profiling of ten medial temporal lobe epilepsy cases which are resistant to the drug and underwent temporal lobectomy. The cases constitutes of patients with intractable complex partial seizure, treated medically and have undergone detailed presurgical evaluation and subjected to surgery for standard temporal lobectomy and amygdalo-hippocampectomy. The spiking areas identified after the electrocorticography will form the test tissues, which compared with the nonspiking areas removed during the surgery, from the same patient. This could probably form one of the appropriate controls, as test and control are from same patient, which eliminates the genome variations that could incur due to the comparison with the tissues from the another patient. Also this could get rid of expression changes due to the treatments undergone by the patient. We performed two color microarray wherein we labled seizure focus (spiking area) with Cy5 and non-seizure region tissues (non-spiking) with Cy3. As a strategy to test the possibility of potential diagnostic biomarkers we are intended to test the differentially regulated molecules in an independent set of epilepsy samples.
2012-12-01 | GSE25453 | GEO
Project description:Mesial temporal lobe epilepsy (mTLE) is a chronic neurological disease characterized by recurrent seizures. The pathogenic mechanisms underlying TLE involve defects in post-transcriptional regulation of gene expression. So far, transcriptome profiles from epileptic tissue have been performed using whole cells, thereby lacking information on RNA localization and function at a subcellular level. In this project, we set out to understand the compartment-specific total RNA profile of human mTLE tissue samples. For this, we had established a protocol to isolate cytoplasmic and nuclear compartments from human hippocampal tissue. Subcellular RNA was isolated from resected hippocampal (HC) and neo-cortical (Cx) tissue from mTLE no hippocampal sclerosis (non-HS) and mTLE HS International League Against Epilepsy (ILAE) Type 1 or mTLE+HS patients and postmortem control tissue. Later, we used total RNA sequencing (RNA-seq) to profile for the distinct RNA localization in mTLE in comparison to postmortem control tissue and identified disease related pathways in individual cell compartments. Here we report the total RNAseq (coding and non-coding) data.
2022-03-31 | GSE186334 | GEO
Project description:Transcriptome studies of brain resections from mesial temporal lobe epilepsy (mTLE) patients revealed a dysregulation of transforming growth factor (TGF)-β, interferon (IFN)-α/β and nuclear factor erythroid 2-related factor 2 (NRF2) pathways among other neuroinflammatory mechanisms. Since ubiquitin-specific proteases (USP), in particular USP15, have been shown to regulate these pathways, we hypothesized that the blockade of USP15 may provide therapeutic relief in treatment-resistant epilepsies. The intrahippocampal kainate mouse model for mTLE, an established model for pharmacoresistant epilepsy was used for validation of USP15 as a therapeutic target. Transgenic mice which constitutively lack USP15 underwent intrahippocampal kainate injections to investigate the impact of USP15 inactivation at the transcriptomic level.
2023-10-12 | E-MTAB-12633 | biostudies-arrayexpress
Project description:Transcriptome studies of brain resections from mesial temporal lobe epilepsy (mTLE) patients revealed a dysregulation of transforming growth factor (TGF)-β, interferon (IFN)-α/β and nuclear factor erythroid 2-related factor 2 (NRF2) pathways among other neuroinflammatory mechanisms. Since ubiquitin-specific proteases (USP), in particular USP15, have been shown to regulate these pathways, we hypothesized that the blockade of USP15 may provide therapeutic relief in treatment-resistant epilepsies. The intrahippocampal kainate mouse model for mTLE, an established model for pharmacoresistant epilepsy was used for validation of USP15 as a therapeutic target. Transgenic mice which inducibly lack USP15 underwent intrahippocampal kainate injections to investigate the impact of USP15 downregulation at the transcriptomic level.
2023-10-12 | E-MTAB-12634 | biostudies-arrayexpress
Project description:We used a systemic inflammatory challenge in animals with chronic mesial temporal lobe epilepsy to identify novel molecular pathways involved in seizure regulation. Mice were first rendered epileptic by a single intrahippocampal injection of kainic acid (KA). After a period of two-three weeks, mice developed spontaneous seizures and then received a single intraperitoneal injection of lipopolysaccharide (LPS) to mimic systemic inflammation, or saline as a control. Gene expression analysis by microarrays was then performed on hippocampal RNA samples extracted 4 and 24 hours after LPS or saline treatment (n=3 samples per treatment group).
2016-05-03 | GSE81024 | GEO
Project description:Mesial temporal lobe epilepsy (mTLE) is a chronic neurological disease characterized by recurrent seizures. The pathogenic mechanisms underlying TLE involve defects in post-transcriptional regulation of gene expression. Previously we have shown the differences in cell compartment specific differential expression of coding transcripts in mTLE hippocampal and cortical samples compared to post-mortem controls (Vangoor et al., MedRxiv. 2021). On the same set of patient samples containing subcellular RNA from resected hippocampal (HC) and neo-cortical (Cx) tissue from mTLE no hippocampal sclerosis (non-HS) and mTLE HS International League Against Epilepsy (ILAE) Type 1 or mTLE+HS patients and postmortem control tissue, we applied small RNA sequencing (smRNA-seq). SmRNA-seq was analyzed for investigating the expression profiles of small non-coding RNA species as microRNAs and transferRNA fragments in human mTLE and control hippocampal tissue.
2024-11-06 | GSE245228 | GEO
Project description:Mesial temporal lobe epilepsy (MTLE) is the most common type of focal seizure disorder. In MTLE, seizures typically originate from a sclerotic hippocampus. Approximately one-third of patients do not respond to anti-seizure drugs and have few effective therapeutic options. Surgery to resect or ablate the affected temporal lobe is one such option, but it is not indicated or adequate for all individuals and can have adverse effects. Here, we report the development of an alternative cell therapy strategy for drug-resistant MTLE. The cell therapeutic is derived from a clinical-grade human embryonic stem cell line, and composed of cryopreserved post-mitotic medial ganglionic eminence (MGE)-type GABAergic inhibitory neurons of a predominantly pallial interneuron lineage. Single-dose intrahippocampal delivery of cryopreserved human pallial interneurons in a chronic mouse model of drug-resistant MTLE resulted in consistent and stable suppression of mesiotemporal seizures, with most animals becoming seizure-free. The grafted human interneurons distributed locally, matured, and persisted in the sclerotic hippocampus throughout the 8.5-month study. Pathological hallmarks of MTLE, such as hippocampal granule cell dispersion and sclerosis, were significantly reduced, and epileptic animal survival rates increased, after administration of the human interneurons. Suppression of seizure activity and amelioration of neuropathology were dose-dependent and suggested a broad therapeutic dosing range. No ectopic tissue or teratoma formation was detected after cell transplantation. Furthermore, behavioral abnormalities were not observed at any dose on a battery of assays. These findings support further development of human pallial MGE-type GABAergic interneuron cell therapy for the treatment of drug-resistant focal epilepsies.
2023-10-10 | GSE208672 | GEO
Project description:Hippocampal sclerosis (HS) is the most common neuropathological finding of medically intractable cases of mesial temporal lobe epilepsy (MTLE), the most common form of partial epilepsy. Within the dentate gyrus, HS may be associated with granule cell dispersion and aberrant mossy fiber sprouting, and these pathological changes are accompanied by a range of molecular changes. In this study, we analyzed the gene expression profiles of dentate granule cells of MTLE patients with and without HS to show that next-generation sequencing methods can produce interpretable genomic data from RNA collected from small homogenous cell populations and to shed light on the transcriptional changes associated with HS. 12 samples of dentate granule cells from patients with mesial tempora lobe epilepsy, 5 with hippocampal sclerosis and 7 without hippocampal sclerosis. 10 samples had replicates.
2016-06-29 | E-GEOD-71058 | biostudies-arrayexpress
Project description:CpG methylation analysis of MeDIP DNA using Agilent Human DNA methylation Microarray slides (G4495A, AMADID 023795) Using methylated DNA immunoprecipitation microarray (MeDIP-chip) and Agilent Human DNA methylation Microarray slides (G4495A, AMADID 023795) we report genomic methylation signatures of tissues resected from Mesial temporal epilepsy (MTLE) and Focal cortical dysplasia (FCD) type II patients undergoing surgery. Control samples were obtained from the non-epileptic post mortem cases without any brain pathology
2018-03-10 | GSE96067 | GEO