title: Chronic intermittent ethanol exposure and its removal induce a different miRNA expression pattern in primary cortical neuronal cultures.
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 10 days of CIE (CIE10) treatment (n = 42 with false discovery rate [FDR] < 0.05 and fold change > 2) and 5 days 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 5 days 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.
authors.affiliation: Department of Pharmacology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, USA.
authors.forename: Yingqiu
authors.initials: Y
authors.lastname: Guo
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Chen
authors.forename: Stephanie
authors.initials: S
authors.lastname: Carreon
authors.forename: Mei
authors.initials: M
authors.lastname: Qiang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects*; D018899:CpG Islands; D000431:Ethanol / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013375:Substance Withdrawal Syndrome / Q000235:genetics* / Q000378:metabolism
chemical_list: D002492:Central Nervous System Depressants; D035683:MicroRNAs; D000431:Ethanol