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Molecular Biology Reports

, Volume 46, Issue 3, pp 2867–2875 | Cite as

Correlation between the epigenetic modification of histone H3K9 acetylation of NR2B gene promoter in rat hippocampus and ethanol withdrawal syndrome

  • Duan Li
  • Yanqing Zhang
  • Yanting Zhang
  • Qi Wang
  • Qin Miao
  • Yahui Xu
  • Jair C. Soares
  • Xiangyang ZhangEmail author
  • Ruiling ZhangEmail author
Original Article
  • 99 Downloads

Abstract

Patients with alcohol use disorder may develop acute ethanol withdrawal syndrome (EWS). Previous studies showed that an epigenetic modification of the N-methyl-d-aspartate (NMDA) receptor, especially NMDA receptor 2B subunit (NR2B), was involved in the pathological process of EWS. However, the relationship between the epigenetic regulation of the NR2B gene in the rat hippocampus region and EWS were inconsistent. The purpose of this study was to explore the role of the histone H3K9 acetylation of the NR2B gene in the rat hippocampus region in EWS. A rat model of chronic ethanol exposure was established. EWS score and the behavioral changes were recorded at different time points. The NR2B expression levels and the histone H3K9 acetylation level in the NR2B gene promoter region were measured using qRT-PCR, Western blot, immunofluorescence, and chromatin immunoprecipitation, respectively. Finally, the relationship between the epigenetic modification of histone H3K9 acetylation of NR2B gene promoter and EWS were examined. Our ultimate results showed that the EWS score was increased at 2 h, peaked at 6 h after withdrawal of ethanol, and reduced to the level parallel to the normal control group at day 3 after ethanol withdrawal. The NR2B mRNA expression and protein levels showed similar patterns. Further correlation analyses indicted that both histone H3K9 acetylation in NR2B gene promoter and the expression levels of NR2B were positively associated with EWS. Our results suggest that chronic ethanol exposure may result in epigenetic modification of histone H3K9 acetylation in NR2B gene promoter in rat hippocampus, and the expression levels of NR2B were found to be positively correlated with ethanol withdrawal syndrome.

Keywords

Chronic ethanol exposure Ethanol withdrawal syndrome Epigenetic modification N-Methyl-d-aspartate receptor N-Methyl-d-aspartate receptor 2B subunit (NR2B) 

Abbreviations

EWS

Ethanol withdrawal syndrome

NMDA

N-Methyl-d-aspartate

NR2B

N-Methyl-d-aspartate receptor 2 B

ChIP

Chromatin immunoprecipitation

qRT-PCR

Quantitative real-time PCR

CIE

Chronic intermittent ethanol

Notes

Funding

This work was supported by the National Natural Science Foundation of China (No. 81471351), Open Program of Henan Key Laboratory of Biological Psychiatry (No. ZDSYS2016007) and the Programs for Science and Technology Development of Henan (No. 172102310499).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

11033_2019_4733_MOESM1_ESM.docx (208 kb)
Supplementary material 1 (DOCX 207 KB)

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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Duan Li
    • 1
    • 2
  • Yanqing Zhang
    • 1
  • Yanting Zhang
    • 1
  • Qi Wang
    • 1
  • Qin Miao
    • 1
  • Yahui Xu
    • 1
  • Jair C. Soares
    • 3
  • Xiangyang Zhang
    • 1
    • 3
    Email author
  • Ruiling Zhang
    • 1
    Email author
  1. 1.The Second Affiliated Hospital of Xinxiang Medical UniversityXinxiangPeople’s Republic of China
  2. 2.Department of Microbiology, School of Basic Medical SciencesXinxiang Medical UniversityXinxiangPeople’s Republic of China
  3. 3.Department of Psychiatry and Behavioral Sciences, McGovern Medical SchoolThe University of Texas Health Science Center at HoustonHoustonUSA

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