Project description:This SuperSeries is composed of the following subset Series:; GSE1831: Temporal analysis of P15 hippocampus in kainate-induced seizures. Koh-2K08NS002068-04; GSE1834: Temporal analysis of hippocampus in kainate-induced seizures. Koh-7K08NS002068-05-3 Experiment Overall Design: Refer to individual Series
Project description:This study aims to investigate age-specific, time-dependent changes in gene expression that may underlie the priming effect of early-life seizures by looking at the sequence of gene expression patterns in the hippocampus at various times following Kainate induced seizures at postnatal day (P) 15.
Project description:This study aims to investigate age-specific, time-dependent changes in gene expression that may underlie the priming effect of early-life seizures by looking at the sequence of gene expression patterns in the hippocampus at various times following Kainate induced seizures at postnatal day (P) 15. Keywords: other
Project description:Mesial temporal lobe epilepsy (MTLE) is the most common medically refractory epilepsy syndrome; kainic acid (KA) induced seizures have been studied as a MTLE model as limbic seizures produced by systemic injections of KA result in a distinctive pattern of neurodegeneration in the hippocampus that resembles human hippocampal sclerosis. In our "2-hit" seizure model, animals subjected to seizures during week 2 of life become more susceptible to seizures later in life and sustain extensive hippocampal neuronal injury after second KA seizures in adulthood. Using high-density oligonucleotide gene arrays, we began to elucidate the molecular basis of this priming effect of early-life seizures and of the age-specific neuroprotection against seizure-induced neuronal injury. We seek to identify target genes for epileptogenesis and cell death by selecting transcripts that are differentially regulated at various times in the P15 and P30 hippocampus. To screen for and identify candidate genes responsible for epileptogenesis and seizure-induced cell death. We hypothesize that active process of cell death signaling and long-term synaptic changes leading to chronic epilepsy is mediated by distinct transcriptional responses in mature brain that are different from those in immature brain. We will select for transcripts that are highly regulated at 1, 6, 24, 72 and 240 hours (h) after KA-induced seizures at P30 compared to P15. These differentially regulated genes will serve as potential target genes for therapeutic intervention. Highly regulated genes identified in our array analysis will then be confirmed by real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Causative roles of select genes will be directly tested by gene silencing using RNA interference technology or by gene delivery using viral vectors.
Project description:It has long been established that in neurological disease models, KA is a potent excitotoxin, mediating acute limbic seizures and long-term morphologic changes in the hippocampus, which are hallmark characteristics seen in temporal lobe epilepsy (i.e. mossy-fiber sprouting, neuronal loss, and reactive gliosis; Ben-Ari and Cossart, 2000). Persuasive clinical evidence employing KA receptor agonists further substantiate the detrimental effects of kainate. For instance, domoic acid (a structural analogue of kainate) has been found to inflict detrimental damage the hippocampus through a real-life outbreak incident of toxic encephalopathy caused by ingestion of mussels contaminated with domoic acid (Pearl et al., 1990). A total of 15 RNA samples were analyzed. Cultured murine primary cortical neurons were treated with 100uM kainate over a time-course of 5h, 15h and 24h (n=3) in addition to the vehicle control (n=6).
Project description:It has long been established that in neurological disease models, KA is a potent excitotoxin, mediating acute limbic seizures and long-term morphologic changes in the hippocampus, which are hallmark characteristics seen in temporal lobe epilepsy (i.e. mossy-fiber sprouting, neuronal loss, and reactive gliosis; Ben-Ari and Cossart, 2000). Persuasive clinical evidence employing KA receptor agonists further substantiate the detrimental effects of kainate. For instance, domoic acid (a structural analogue of kainate) has been found to inflict detrimental damage the hippocampus through a real-life outbreak incident of toxic encephalopathy caused by ingestion of mussels contaminated with domoic acid (Pearl et al., 1990).
