Evidence map›Paper›PMID 40534269›Full record

ArticleCNS neuroscience & therapeutics2025

Vagus Nerve Stimulation Inhibits DNA and RNA Methylation in a Rat Model of Pilocarpine-Induced Temporal Lobe Epilepsy.

Zhonghua Xiong, Jing Zhang, Qinqin Deng, Minghui Wang, Tianfu Li

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Article in CNS neuroscience & therapeutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

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4 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

5 authors.

Zhonghua XiongDepartment of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing, China.ORCID 0000-0001-9488-9039
Jing ZhangDepartment of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing, China.
Qinqin DengDepartment of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing, China.
Minghui WangDepartment of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing, China.
Tianfu LiDepartment of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing, China.ORCID 0000-0002-0883-4988

Funding

National Key Research and Development Program of China 2021YFC2401203National Natural Science Foundation of China 81571275
6 · The paper itself

Abstract

introductionVagus nerve stimulation (VNS) represents a clinically approved neuromodulatory intervention for managing refractory epilepsy. VNS exhibits antiepileptogenic effects in animal models; the molecular and cellular mechanisms driving these effects have yet to be fully elucidated. Epigenetic alterations, including DNA and RNA methylation, are implicated in the pathogenesis of epilepsy. This study was designed to examine whether VNS inhibits DNA/RNA methylation in temporal lobe epilepsy.

methodsA rat model of temporal lobe epilepsy induced by intraperitoneal injection of lithium chloride-pilocarpine was used. Naïve control group, Pilo groups (8 and 12 weeks after pilocarpine respectively), VNS group (VNS stimulation for 4w and 8w respectively), and Sham group (VNS off control group, with VNS implanted but not turned on for 4w and 8w respectively). The rats were monitored by video-EEG. DNMT1 (DNA methyltransferase-1), DNMT3A (methyltransferase-3A), 5-hmC (5-hydroxymethyl-cytosine), 5-mC (5-methyl-cytosine), METTL3 (RNA methyltransferase like 3), METTL14 (RNA methyltransferase like 14) were quantified via immunohistochemistry and Western blot.

resultsPilocarpine-induced epileptic animals were characterized by overexpression of 5-mC, DNMT1, DNMT3A, METTL3, and METTL14, and a decrease of 5-hmC. Compared to the Pilo group, VNS significantly inhibited the overexpression of 5-mC, DNMT1, DNMT3A, METTL3, and METTL14, reduced the downregulation of 5-hmC, and attenuated spontaneous recurrent seizures (SRSs).

conclusionsWe conclude that VNS reduces the number of SRSs in a rat model of epilepsy, concurrently reducing the expression of 5-mC, DNMT1, DNMT3A, METTL3, and METTL14, as well as the increase of 5-hmC. These findings suggest that epigenetic modifications, specifically the suppression of DNA and RNA methylation, could constitute a potential target of VNS-mediated antiepileptic effects.

Indexed as

DNA MethylationEpilepsy, Temporal LobeVagus Nerve StimulationAnimalsDisease Models, AnimalMaleMuscarinic AgonistsPilocarpineRatsRats, Sprague-DawleyRNA MethylationMuscarinic AgonistsPilocarpine5‐hmC5‐mCepilepsyMETTL14METTL3vagus nerve stimulation

Identifiers

PMID40534269
PMCPMC12177201

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.