Project description:Explore DNA methylation in chronic epilepsy and its relationship to gene expression. Examination of expression changes in pilocarpine-treated rats compared to controls and pilocarpine-treated rats on a ketogenic diet.
Project description:Explore DNA methylation in chronic epilepsy and its relationship to gene expression. Examination of methylation changes in pilocarpine-treated rats compared to controls and pilocarpine-treated rats on a ketogenic diet.
Project description:Profiling of LncRNAs and mRNAs in the mouse pilocarpine model in specific brain regions, the hippocampus and cortex, and compared the results to those of the control mouse.
Project description:Anti-epileptogenic agents that prevent the development of epilepsy following a brain insult remain the holy grail of epilepsy therapeutics. In order to identify such drugs, it is necessary to first understand the cellular and molecular events that underlie the epileptogenic process, from initial insult to the onset of spontaneous recurrent seizures. We have employed a label-free proteomic approach that allows quantification of large numbers of brain-expressed proteins in a single analysis in the well-established kainate (KA) mouse (C57BL/6J) model of epileptogenesis. In addition, we have incorporated two putative antiepileptogenic drugs, PSD95BP and 1400W, to give an insight into how such agents might ameliorate the epileptogenesis. The test drugs were administered at appropriate time-points after induction of status epilepticus (SE) and animals were euthanized at 7 days, their hippocampi removed, and subjected to LC-MS/MS analysis. A total of 2,579 proteins were identified; their normalized abundance was compared between treatment groups using ANOVA, with correction for multiple testing by false discovery rate. Significantly altered proteins were subjected to gene ontology analysis to look for enrichment of specific biological processes. KA-induced SE was most robustly associated with an increase in proteins involved in neuroinflammation, oxidative stress, cell-cell interactions and synaptic plasticity. Treatment with PSD95BP (Tat-NR2B9c) or an iNOS inhibitor, 1400W modulated several of these proteins. Our observations require validation in a larger-scale investigation, with candidate proteins explored in more detail. Nevertheless, this study has identified several mechanisms by which epilepsy might be developed and several targets for novel drug development.
Project description:Explore DNA methylation in traumatic brain injury model of epilepsy and its relationship to gene expression. Examination of expression changes in stimulated rats compared to sham operated animals in traumatic brain injury model of epilepsy.
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.
Project description:Global expression profiling of epileptogenesis has been confounded by variability across laboratories, epilepsy models, tissue sampled and experimental platforms, with the result that very few genes demonstrate consistent expression changes. The present study minimizes these confounds by combining Affymetrix microarray datasets from seven laboratories, using three status epilepticus (SE) models of epilepsy in rats (pilocarpine, kainate, self-sustained SE or SSSE) and the rat kindling model. Total RNA was harvested from laser-captured dentate granule cells from 6 rats at three times during the early-to-mid latent phase that precedes epilepsy symptoms in the SE models (1, 3 and 10 days after SE), or 24 hr after the first stage 2, stage 4 and stage 5 seizure in the kindling model. Each epilepsy model was studied in two independent laboratories except SSSE. The initial goals of this study were to a) identify model-independent transcriptional changes in dentate granule cells that could point to novel intervention targets for epileptogenesis, b) characterize the basal transcriptional profile of dentate granule cells, and c) identify genes that have highly variable expression. Each experimental group consists of 6 rats (biological replicates) from one laboratory at a single time point, except for the SSSE group (6 at day 1 after SSSE, 5 controls and at day 3 after SSSE, 4 at day 10). Thus granule cells were harvested from 164 rats.