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Neurochemical Research

, Volume 43, Issue 10, pp 2000–2007 | Cite as

RASgrf1, a Potential Methylatic Mediator of Anti-epileptogenesis?

  • Yi Bao
  • Xiaoni Chen
  • Liang WangEmail author
  • Jixiu Zhou
  • Xinwei Fu
  • Xuefeng Wang
  • Zheng XiaoEmail author
Original Paper

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.

Keywords

RASgrf1 DNA methylation RG108 Epilepsy Epileptogenesis 

Notes

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant Numbers 81071040, 81471320).

Compliance with Ethical Standards

Conflict of interest

None of the authors has any conflicts of interest to disclose.

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of NeurologyThe First Affiliated Hospital of Chongqing Medical UniversityChongqingChina
  2. 2.Department of NeurologyXi’an No.3 HospitalXianChina
  3. 3.Department of NeurologyThe People’s Hospital of Rongchang DistrictChongqingChina
  4. 4.Department of NeurologyThe Third Hospital of MianyangMianyangChina

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