Abstract：
:Epileptogenesis, induced by status epilepticus (SE), is a chronic process, and intervention in this progress may prevent chronic epilepsy. It has been proposed that DNA methylation might be related with epileptogenesis. RASgrf1 has a differentially methylated region at the promoter which can silence gene expression. We have previously observed the down-regulation of RASgrf1 in epilepsy patients and proved that hypermethylation of RASgrf1 reaches maximal level at the latent period in mice after kainate-induced SE (KA mice), with corresponding alteration of RASgrf1 expression. In the present study, N-phthalyl-L-tryptophan (RG108), a DNA methyltransferase inhibitor, was applied in KA mice at latent phase and the behavior, electroencephalogram and pathological changes were observed in chronic phase. Methylation and expression of RASgrf1 were determined by polymerase chain reaction (PCR), western blotting, and bisulfite sequencing PCR. The results showed that the incidence of spontaneous recurrent seizures (SRS) was significantly lower in the RG108 group than the normal saline (NS) group. Subgroup analysis showed significant hypermethylation and lower expression of RASgrf1 in the RG108-SRS subgroup and the NS-SRS subgroup but not in the RG108-NSRS (no SRS) subgroup and the NS-NSRS subgroup compared with the control group. No significant difference was found between the RG108-SRS and NS-SRS subgroups. Meanwhile, hippocampal neuronal loss was observed in RG108-SRS and NS-SRS subgroups. We thus demonstrated that RG108 could modify the progression of epileptogenesis after KA induced SE and prevent chronic epilepsy. Meanwhile, hypermethylation of RASgrf1 after KA induced SE could be reversed with corresponding changes of RASgrf1 expression. Additionally, we speculated that RASgrf1 might be a potential epigenetic mediator in epileptogenesis and chronic epilepsy.
journal_name
Neurochem Resjournal_title
Neurochemical researchauthors
Bao Y,Chen X,Wang L,Zhou J,Fu X,Wang X,Xiao Zdoi
10.1007/s11064-018-2621-9subject
Has Abstractpub_date
2018-10-01 00:00:00pages
2000-2007issue
10eissn
0364-3190issn
1573-6903pii
10.1007/s11064-018-2621-9journal_volume
43pub_type
杂志文章abstract：:The effects of acute lorazepam challenges on plasma (p) HVA, MHPG, and 5-HIAA, and their relationship to drug-induced cognitive and motor deficits and the apolipoprotein (APOE)-epsilon4 allele were examined. Eighteen healthy elderly (8 epsilon4 carriers) received placebo or acute oral lorazepam doses (0.5 mg or 1 mg) ...
journal_title：Neurochemical research
pub_type： 临床试验,杂志文章,随机对照试验
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更新日期：2004-07-01 00:00:00
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journal_title：Neurochemical research
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更新日期：2006-02-01 00:00:00
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pub_type： 杂志文章,评审
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doi：10.1007/s11064-008-9832-4
更新日期：2009-05-01 00:00:00
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pub_type： 杂志文章
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更新日期：2013-09-01 00:00:00
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journal_title：Neurochemical research
pub_type： 杂志文章,评审
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更新日期：1990-02-01 00:00:00
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journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/BF00972471
更新日期：1994-11-01 00:00:00
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pub_type： 杂志文章
doi：10.1007/s11064-010-0391-0
更新日期：2011-07-01 00:00:00
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journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/BF00965136
更新日期：1982-08-01 00:00:00
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pub_type： 杂志文章
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更新日期：2020-01-01 00:00:00
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更新日期：1997-09-01 00:00:00
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pub_type： 杂志文章
doi：10.1007/s11064-009-9951-6
更新日期：2009-09-01 00:00:00
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pub_type： 杂志文章
doi：10.1007/s11064-008-9830-6
更新日期：2009-05-01 00:00:00
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pub_type： 杂志文章,评审
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更新日期：2012-04-01 00:00:00
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更新日期：2004-12-01 00:00:00
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journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-015-1805-9
更新日期：2016-02-01 00:00:00
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pub_type： 杂志文章
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更新日期：1992-04-01 00:00:00
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journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-014-1236-z
更新日期：2014-02-01 00:00:00
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journal_title：Neurochemical research
pub_type： 杂志文章
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更新日期：1988-04-01 00:00:00
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pub_type： 杂志文章
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更新日期：2017-06-01 00:00:00
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journal_title：Neurochemical research
pub_type： 杂志文章
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更新日期：1987-03-01 00:00:00
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pub_type： 杂志文章
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更新日期：2004-11-01 00:00:00
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pub_type： 杂志文章
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更新日期：1995-01-01 00:00:00
