Alterations in mRNA levels in the dentate gyrus in epileptic rats
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ABSTRACT: Analysis of the dentate gyrus of amygdala electrical stimulation model of temporal lobe epilepsy. Results provide insight into the molecular mechanism underlying epileptogenesis. This study was designed to estimate changes in gene expression levels after 7 and 30 days after electrical stimulation of amygdala as a model of temporal lobe epilepsy. The advantage of this study is time matched control (sham operated animals sacrificed at the same age as stimulated animals).
Project description:Analysis of the dentate gyrus of amygdala electrical stimulation model of temporal lobe epilepsy. Results provide insight into the molecular mechanism underlying epileptogenesis. This study was designed to estimate changes in miRNA expression levels after 7, 14, 30 and 90 days after electrical stimulation of amygdala as a model of temporal lobe epilepsy. The advantage of this study is time matched control (sham operated animals sacrificed at the same age as stimulated animals).
Project description:Analysis of the dentate gyrus of amygdala electrical stimulation model of temporal lobe epilepsy. Results provide insight into the molecular mechanism underlying epileptogenesis.
Project description:Analysis of the dentate gyrus of amygdala electrical stimulation model of temporal lobe epilepsy. Results provide insight into the molecular mechanism underlying epileptogenesis.
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
Project description:Background Semantic dementia (SD) is a subtype of frontotemporal dementia (FTD) characterized by language deficits due to severe temporal lobe degeneration. The consistent neuropathological diagnosis is FTD-TDP subtype C, with characteristic round TDP-43 protein inclusions in the dentate gyrus. Despite this striking clinicopathological concordance, the pathogenic mechanisms are largely unexplained forestalling the development of targeted therapeutics. Methods We carried out laser capture microdissection of the dentate gyrus of 15 SD patients and 17 non-demented controls, and assessed relative protein abundance changes by label-free quantitative mass spectrometry. To identify SD specific proteins, we compared our results to eight other FTD and Alzheimer’s disease (AD) proteomic datasets of cortical brain tissue, parallel with functional enrichment analyses and protein-protein interactions (PPI). Results Of the total 5,354 quantified proteins, 151 showed differential abundance (FDR<1%) in SD patients. Seventy-two proteins were previously found altered with the same directional change in at least one FTD/AD proteomic study, while 79 proteins were considered as showing potentially SD specific dysregulation. Functional enrichment indicated an overrepresentation of pathways related to the immune response, metabolic processes, and cell-junction assembly. PPI analysis highlighted a cluster of interacting proteins associated with adherens junction and cadherin binding– the cadherin-catenin complex. Multiple proteins in this complex showed strong and apparent specific upregulation in SD, including β-catenin (CTNNB1), γ-catenin (JUP), and N-cadherin (CDH2). Conclusions We discovered an increase of cell adhesion proteins in SD specifically constituting the cadherin-catenin complex at the synaptic membrane, essential for synaptic signaling. Although further validation is warranted, we anticipate that these findings will help unravel the disease processes underlying SD.
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.
Project description:Explore DNA methylation in focal amygdala stimulation model of epilepsy and its relationship to gene expression. Examination of methylation changes in stimulated rats compared to sham operated animals in focal amygdala stimulation model of epilepsy.
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
Project description:Explore DNA methylation in focal amygdala stimulation model of epilepsy and its relationship to gene expression. Examination of expression changes in stimulated rats compared to sham operated animals in focal amygdala stimulation model of epilpesy.