Open AccessProlonged febrile seizures induce inheritable memory deficits in rats through DNA methylation
Author(s) -
Dai YunJian,
Wu DengChang,
Feng Bo,
Chen Bin,
Tang YangShun,
Jin MiaoMiao,
Zhao HuaWei,
Dai HaiBin,
Wang Yi,
Chen Zhong
Publication year - 2019
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.13088
Subject(s) - epigenetics , dna methylation , reelin , offspring , dnmt1 , neuroscience , psychology , memory impairment , dna methyltransferase , cognition , biology , gene , pregnancy , genetics , gene expression , receptor
Summary Aims Febrile seizures (FSs) are the most common types of seizures in young children. However, little is known whether the memory deficits induced by early‐life FSs could transmit across generations or not. Methods The memory functions of different generations of FS rats were behaviorally evaluated by morris water maze, inhibitory avoidance task, and contextual fear conditioning task. Meanwhile, molecular biology and pharmacological methods were used to investigate the role of DNA methylation in transgenerational transmission of memory defects. Results Prolonged FSs in infant rats resulted in memory deficits in adult and transgenerationally transmitted to next generation, which was mainly through mothers. For these two generations, DNA methyltransferase (DNMT) 1 was upregulated, leading to transcriptional inhibition of the synaptic plasticity protein reelin but not the memory suppressor protein phosphatase 1. DNMT inhibitors prevented the high expression of DNMT1 and hypermethylation of reelin gene and reversed the transgenerationally memory deficits. In addition, enriched environment in juvenile rats rescued memory deficits induced by prolonged FSs. Conclusions Our study demonstrated early experience of prolonged FSs led to memory deficits in adult rats and their unaffected offspring, which involved epigenetic mechanisms, suggesting early environmental experiences had a significant impact on the transgenerational transmission of neurological diseases.