Hippocampal transcriptome after status epilepticus in mice rendered seizure damage-tolerant by epileptic preconditioning features suppressed calcium and neuronal excitability pathways

Jiménez-Mateos, Eva M.; Hatazaki, Seiji; Johnson, Martha B.; Bellver-Estelles, Carmen; Mouri, Genshin; Bonner, Caroline; Prehn, Jochen H.M.; Meller, Robert; Simon, Roger P.; Henshall, David C.

doi:10.1016/j.nbd.2008.08.008

Cited by 63 publications

(81 citation statements)

References 50 publications

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“…An interrogation of the previously reported genes differentially downregulated in epileptic tolerance (Jimenez-Mateos et al, 2008) found two of the differentially hypermethylated genes in tolerance: groups. Also apparent is a smaller subset of genomic locations that are differentially methylated in injury and tolerance groups and some regions in which there is a clear difference in tolerance from both injury and control.…”

Section: Promoter Methylation Profiles After Se and Epileptic Tolerancementioning

confidence: 89%

“…Animal experiments were performed as described previously (Hatazaki et al, 2007;Jimenez-Mateos et al, 2008) in accordance with the European Communities Council Directive (86/609/EEC) and were reviewed and approved by the Research Ethics Committee of the Royal College of Surgeons in Ireland, under license from the Department of Health, Dublin, Ireland. Adult male mice (C57BL/6, 20 -25 g) were obtained from Harlan.…”

Section: Methodsmentioning

confidence: 99%

“…We first sought to establish the presence of DNA methyltransferases in the CA3 subfield, which is the site of major neuronal death after intra-amygdala KA-induced SE and which is protected in animals given seizure preconditioning (Hatazaki et al, 2007;Jimenez-Mateos et al, 2008). We were also interested in whether seizure preconditioning caused changes to levels of these genes that might influence how and whether methylation differences occurred when SE is applied.…”

Section: Dna Methyltransferase Expression In the Ca3 Subfield Of The mentioning

confidence: 99%

“…In recent years, our understanding of the molecular processes underlying tolerance has been assisted by microarray profiling, which has revealed large-scale, genomic reprogramming of the response to injury (Stenzel-Poore et al, 2007;Johnson and Simon, 2009). In epileptic tolerance, 73% of the 565 differentially expressed genes in the hippocampus were downregulated (Jimenez-Mateos et al, 2008). This included genes that encode ion channels, excitatory neurotransmitter receptors, and calcium signaling components, indicating that suppression of excitability-and excitotoxicity-related pathways is the main transcriptional phenotype of epileptic tolerance (Jimenez-Mateos et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

“…In epileptic tolerance, 73% of the 565 differentially expressed genes in the hippocampus were downregulated (Jimenez-Mateos et al, 2008). This included genes that encode ion channels, excitatory neurotransmitter receptors, and calcium signaling components, indicating that suppression of excitability-and excitotoxicity-related pathways is the main transcriptional phenotype of epileptic tolerance (Jimenez-Mateos et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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Differential DNA Methylation Patterns Define Status Epilepticus and Epileptic Tolerance

Miller-Delaney¹,

Das²,

Sano³

et al. 2012

J. Neurosci.

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Prolonged seizures (status epilepticus) produce pathophysiological changes in the hippocampus that are associated with large-scale, wide-ranging changes in gene expression. Epileptic tolerance is an endogenous program of cell protection that can be activated in the brain by previous exposure to a non-harmful seizure episode before status epilepticus. A major transcriptional feature of tolerance is gene downregulation. Here, through methylation analysis of 34,143 discrete loci representing all annotated CpG islands and promoter regions in the mouse genome, we report the genome-wide DNA methylation changes in the hippocampus after status epilepticus and epileptic tolerance in adult mice. A total of 321 genes showed altered DNA methylation after status epilepticus alone or status epilepticus that followed seizure preconditioning, with Ͼ90% of the promoters of these genes undergoing hypomethylation. These profiles included genes not previously associated with epilepsy, such as the polycomb gene Phc2. Differential methylation events generally occurred throughout the genome without bias for a particular chromosomal region, with the exception of a small region of chromosome 4, which was significantly overrepresented with genes hypomethylated after status epilepticus. Surprisingly, only few genes displayed differential hypermethylation in epileptic tolerance. Nevertheless, gene ontology analysis emphasized the majority of differential methylation events between the groups occurred in genes associated with nuclear functions, such as DNA binding and transcriptional regulation. The present study reports select, genome-wide DNA methylation changes after status epilepticus and in epileptic tolerance, which may contribute to regulating the gene expression environment of the seizure-damaged hippocampus.

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Section: Promoter Methylation Profiles After Se and Epileptic Tolerancementioning

confidence: 89%

Section: Methodsmentioning

confidence: 99%

Section: Dna Methyltransferase Expression In the Ca3 Subfield Of The mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Differential DNA Methylation Patterns Define Status Epilepticus and Epileptic Tolerance

Miller-Delaney¹,

Das²,

Sano³

et al. 2012

J. Neurosci.

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Transcriptomic analysis of dorsal and ventral subiculum after induction of acute seizures by electric stimulation of the perforant pathway in rats

et al. 2022

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Preconditioning is a mechanism in which injuries induced by non‐lethal hypoxia or seizures trigger cellular resistance to subsequent events. Norwood et al., in a 2010 study, showed that an 8‐h‐long period of electrical stimulation of the perforant pathway in rats is required for the induction of hippocampal sclerosis. However, in order to avoid generalized seizures, status epilepticus (SE), and death, a state of resistance to seizures must be induced in the hippocampus by a preconditioning paradigm consisting of two daily 30‐min stimulation periods. Due to the importance of the subiculum in the hippocampal formation, this study aims to investigate differential gene expression patterns in the dorsal and ventral subiculum using RNA‐sequencing, after induction of a preconditioning protocol by electrical stimulation of the perforant pathway. The dorsal (dSub) and ventral (vSub) subiculum regions were collected by laser‐microdissection 24 h after preconditioning protocol induction in rats. RNA sequencing was performed in a Hiseq 4000 platform, reads were aligned using the STAR and DESEq2 statistics package was used to estimate gene expression. We identified 1176 differentially expressed genes comparing control to preconditioned subiculum regions, 204 genes were differentially expressed in dSub and 972 in vSub. The gene ontology enrichment analysis showed that the most significant common enrichment pathway considering up‐regulated genes in dSub and vSub was steroid metabolism. In contrast, the most significant enrichment pathway considering down‐regulated genes in vSub was axon guidance. Our results indicate that preconditioning induces changes in the expression of genes related to synaptic reorganization, increased cholesterol metabolism, and astrogliosis in both dSub and vSub. Both regions also presented a decrease in the expression of genes related to glutamatergic transmission and an increase in expression of genes related to complement system activation and GABAergic transmission. The down‐regulation of proapoptotic and axon guidance genes in the ventral subiculum suggests that preconditioning may induce a neuroprotective environment in this region.

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Preconditioning for Epilepsy

Henshall

Jiménez-Mateos

2012

Innate Tolerance in the CNS

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Hippocampal transcriptome after status epilepticus in mice rendered seizure damage-tolerant by epileptic preconditioning features suppressed calcium and neuronal excitability pathways

Cited by 63 publications

References 50 publications

Differential DNA Methylation Patterns Define Status Epilepticus and Epileptic Tolerance

Differential DNA Methylation Patterns Define Status Epilepticus and Epileptic Tolerance

Transcriptomic analysis of dorsal and ventral subiculum after induction of acute seizures by electric stimulation of the perforant pathway in rats

Preconditioning for Epilepsy

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