Chronic Intermittent Ethanol Exposure and Its Removal Induce a Different miRNA Expression Pattern in Primary Cortical Neuronal Cultures

Yingqiu Guo, Yongxin Chen, Stephanie Carreon, Mei Qiang

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Background: Increasing evidence indicates that repeated exposure to and withdrawal from alcohol can result in persistent molecular and cellular adaptations. One molecular adaptation that occurs is the regulation of gene expression, which is thought to lead to the functional alterations that characterize addiction: tolerance, dependence, withdrawal, craving, and relapse. MicroRNAs (miRNAs) have been recently identified as master regulators of gene expression through post-transcriptional regulation. However, the role of miRNAs in the neuroadaptations after alcohol removal has not yet been directly addressed. Methods: We employed a chronic intermittent ethanol (CIE) model in primary cortical neuronal cultures to examine the global extent of differential miRNA expression using a TaqMan real-time PCR miRNA array. Results: Sixty-two miRNAs were differentially expressed after 10days of CIE (CIE10) treatment (n=42 with false discovery rate [FDR]<0.05 and fold change>2) and 5days post-CIE (P5) treatment (n=26) compared with untreated control values. Compared to CIE10, ethanol (EtOH) removal experience in P5 induced a distinct expression pattern, including 20 differentially expressed miRNAs, which did not exhibit a significant change at CIE10. The predicted target molecules of EtOH removal-induced miRNAs function mainly in the regulation of gene transcription, but also function in neuron differentiation, embryonic development, protein phosphorylation, and synaptic plasticity. Interestingly, some of the miRNAs differentially expressed 5days after CIE treatment were found to cluster on chromosomes near CpG islands, suggesting that they share functional similarity by targeting alcohol-related genes. Conclusions: Taken together, these results suggest a potential role of differentially expressed miRNAs in mediating EtOH removal-related phenotypes.

Original languageEnglish (US)
Pages (from-to)1058-1066
Number of pages9
JournalAlcoholism: Clinical and Experimental Research
Volume36
Issue number6
DOIs
StatePublished - Jun 1 2012

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Keywords

  • Alcohol
  • Chronic Intermittent Ethanol
  • MicroRNAs
  • Neuroadaptation
  • Neuronal Culture

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

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