Temporal analysis of P15 and P30 hippocampi in kainate-induced seizures
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE4236 | GEO | 2006/02/14
SECONDARY ACCESSION(S): PRJNA94893
REPOSITORIES: GEO
Similar Datasets
Project description:Temporal analysis of P15 and P30 hippocampi in kainate-induced seizures
| PRJNA94893 | ENA
Project description:Early childhood convulsions have been correlated with hippocampal neuron loss in patients with intractable temporal lobe epilepsy. Using a "two-hit" rat seizure model, we have shown that animals subjected to kainate (KA)- or hypoxia-induced seizures during early postnatal period showed no cell death, yet sustained more extensive neuronal death after second seizures in adulthood. An early life seizure, without causing overt cellular injury, predisposes the brain to the damaging effect of seizures in later life. Cellular and molecular changes that accompany early seizures and that lead to subsequent epileptogenesis and increased susceptibility to seizure-induced neuronal injury, however, remain poorly understood. We propose to investigate age-specific, time-dependent changes in gene expression that may underlie this priming effect of early-life seizures. We will determine the sequence of gene expression pattern in the hippocampus at various times following KA induced seizures at postnatal day (P) 15. Previous studies have shown that AMPA receptor subtype of glutamate receptors play a crucial role in the age-specific vulnerability and in the long-term epileptogenic effects of perinatal hypoxia seizures. We found that AMPA receptor antagonists block the increased susceptibility caused by early life seizures to later seizures and seizure-induced brain damage. We hypothesize that an alteration of AMPA receptor composition is one of many changes caused by early-life seizures that leads to an increase in Ca2+ permeability, which then results in cascade of downstream events and modifies array of gene expression that promote epileptogenesis and susceptibility to neuronal death in later life. We will examine three time points: 1hr, 72 hr, and 15 days following systemic KA-induced seizures at P15 as we have previously observed structural changes within the hippocampus at these time points. Within an hour of KA seizures, a marked swelling of dendrites, disassembly of dendritic microtubules and glycogen depletion are observed by electron microscopy. Within 5 days, basal dendrites of CA3 hippocampal pyramidal neurons show abnormal spine morphology and decreased branching pattern. 15 days after the seizures, aberrant growth of mossy fibers in the CA3 stratum oriens is observed in animals exposed to KA. Ten hippocampi will be pooled from five animals treated with KA (3mg/kg i.p.) and from five littermate controls injected with PBS. Animals will be decapitated and hippocampi will be rapidly dissected from the brain, flash frozen in liquid nitrogen, and stored at -80C until extraction of total RNA, which will be sent to the center. We will provide 4 tissue samples-2 controls and 2 KA, each a pool of five animals - for each time points. Mixing tissues from multiple rats will normalize single nucleotide polymorphisms and tissue heterogeneity. Keywords: time-course
2004-10-14 | GSE1831 | GEO
Project description:Early childhood convulsions have been correlated with hippocampal neuron loss in patients with intractable temporal lobe epilepsy. Using a "two-hit" rat seizure model, we have shown that animals subjected to kainate (KA)- or hypoxia-induced seizures during early postnatal period showed no cell death, yet sustained more extensive neuronal death after second seizures in adulthood. An early life seizure, without causing overt cellular injury, predisposes the brain to the damaging effect of seizures in later life. Cellular and molecular changes that accompany early seizures and that lead to subsequent epileptogenesis and increased susceptibility to seizure-induced neuronal injury, however, remain poorly understood. We propose to investigate age-specific, time-dependent changes in gene expression that may underlie this priming effect of early-life seizures. We will determine the sequence of gene expression pattern in the hippocampus at various times following KA induced seizures at postnatal day (P) 15. Previous studies have shown that AMPA receptor subtype of glutamate receptors play a crucial role in the age-specific vulnerability and in the long-term epileptogenic effects of perinatal hypoxia seizures. We found that AMPA receptor antagonists block the increased susceptibility caused by early life seizures to later seizures and seizure-induced brain damage. We hypothesize that an alteration of AMPA receptor composition is one of many changes caused by early-life seizures that leads to an increase in Ca2+ permeability, which then results in cascade of downstream events and modifies array of gene expression that promote epileptogenesis and susceptibility to neuronal death in later life. We will examine three time points: 1hr, 72 hr, and 15 days following systemic KA-induced seizures at P15 as we have previously observed structural changes within the hippocampus at these time points. Within an hour of KA seizures, a marked swelling of dendrites, disassembly of dendritic microtubules and glycogen depletion are observed by electron microscopy. Within 5 days, basal dendrites of CA3 hippocampal pyramidal neurons show abnormal spine morphology and decreased branching pattern. 15 days after the seizures, aberrant growth of mossy fibers in the CA3 stratum oriens is observed in animals exposed to KA. Ten hippocampi will be pooled from five animals treated with KA (3mg/kg i.p.) and from five littermate controls injected with PBS. Animals will be decapitated and hippocampi will be rapidly dissected from the brain, flash frozen in liquid nitrogen, and stored at -80C until extraction of total RNA, which will be sent to the center. We will provide 4 tissue samples-2 controls and 2 KA, each a pool of five animals - for each time points. Mixing tissues from multiple rats will normalize single nucleotide polymorphisms and tissue heterogeneity.
2008-06-11 | E-GEOD-1831 | biostudies-arrayexpress
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. Keywords: time-course
2004-10-14 | GSE1834 | GEO
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
2007-10-10 | E-GEOD-4236 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2019-11-15 | GSE133930 | GEO
Project description:Acquired epilepsy (i.e., after an insult to the brain) is often considered to be a progressive disorder, and the nature of this hypothetical progression remains controversial. Antiepileptic drug treatment necessarily confounds analyses of progressive changes in human patients with acquired epilepsy. Here, we describe experiments testing the hypothesis that development of acquired epilepsy begins as a continuous process of increased seizure frequency (i.e., proportional to probability of a spontaneous seizure) that ultimately plateaus. Using nearly continuous surface cortical and bilateral hippocampal recordings with radiotelemetry and semiautomated seizure detection, the frequency of electrographically recorded seizures (both convulsive and nonconvulsive) was analyzed quantitatively for approximately 100 d after kainate-induced status epilepticus in adult rats. The frequency of spontaneous recurrent seizures was not a step function of time (as implied by the "latent period"); rather, seizure frequency increased as a sigmoid function of time. The distribution of interseizure intervals was nonrandom, suggesting that seizure clusters (i.e., short interseizure intervals) obscured the early stages of progression, and may have contributed to the increase in seizure frequency. These data suggest that (1) the latent period is the first of many long interseizure intervals and a poor measure of the time frame of epileptogenesis, (2) epileptogenesis is a continuous process that extends much beyond the first spontaneous recurrent seizure, (3) uneven seizure clustering contributes to the variability in occurrence of epileptic seizures, and (4) the window for antiepileptogenic therapies aimed at suppressing acquired epilepsy probably extends well past the first clinical seizure.
| S-EPMC2897752 | biostudies-literature
Project description:The cAMP responsive element binding protein (CREB) pathway has been involved in two major cascades of gene expression regulating neuronal function. The first one presents CREB as a critical component of the molecular switch that control longlasting forms of neuronal plasticity and learning. The second one relates CREB to neuronal survival and protection. To investigate the role of CREB-dependent gene expression in neuronal plasticity and survival in vivo, we generated bitransgenic mice expressing A-CREB, an artificial peptide with strong and broad inhibitory effect on the CREB family, in forebrain neurons in a regulatable manner. The expression of ACREB in hippocampal neurons impaired L-LTP, reduced intrinsic excitability and the susceptibility to induced seizures, and altered both basal and activity-driven gene expression. In the long-term, the chronic inhibition of CREB function caused severe loss of neurons in the CA1 subfield as well as in other brain regions. Our experiments confirmed previous findings in CREB deficient mutants and revealed new aspects of CREB-dependent gene expression in the hippocampus supporting a dual role for CREB-dependent gene expression regulating intrinsic and synaptic plasticity and promoting neuronal survival. manufacturer's protocol.
2009-01-12 | GSE14320 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-04-02 | E-GEOD-63580 | biostudies-arrayexpress
Project description:Status epilepticus (SE) is a condition in which seizures are not self-terminating and thereby pose a serious threat to the patient's life. The molecular mechanisms underlying SE are likely heterogeneous and not well understood. Here, we reveal a role for the RNA-binding protein Fragile X-Related Protein 2 (FXR2P) in SE. Fxr2 KO mice display reduced sensitivity specifically to kainic acid-induced SE. Immunoprecipitation of FXR2P coupled to next-generation sequencing of associated mRNAs shows that FXR2P targets are enriched in genes that encode glutamatergic post-synaptic components. Of note, the FXR2P target transcriptome has a significant overlap with epilepsy and SE risk genes. In addition, Fxr2 KO mice fail to show sustained ERK1/2 phosphorylation induced by KA and present reduced burst activity in the hippocampus. Taken together, our findings show that the absence of FXR2P decreases the expression of glutamatergic proteins, and this decrease might prevent self-sustained seizures.
| S-EPMC8024897 | biostudies-literature