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Brain Sci. 2013 May 03;3(2):744-56. doi: 10.3390/brainsci3020744.

Differential Effects of Chronic and Chronic-Intermittent Ethanol Treatment and Its Withdrawal on the Expression of miRNAs.

Brain sciences

Gretchen van Steenwyk, Paulina Janeczek, Joanne M Lewohl

Affiliations

  1. Griffith Health Institute, School of Medical Sciences, Griffith University, Gold Coast Campus, Southport QLD 4215, Australia. [email protected].
  2. Griffith Health Institute, School of Medical Sciences, Griffith University, Gold Coast Campus, Southport QLD 4215, Australia. [email protected].
  3. Griffith Health Institute, School of Medical Sciences, Griffith University, Gold Coast Campus, Southport QLD 4215, Australia. [email protected].

PMID: 24961422 PMCID: PMC4061861 DOI: 10.3390/brainsci3020744

Abstract

Chronic and excessive alcohol misuse results in changes in the expression of selected miRNAs and their mRNA targets in specific regions of the human brain. These expression changes likely underlie the cellular adaptations to long term alcohol misuse. In order to delineate the mechanism by which these expression changes occur, we have measured the expression of six miRNAs including miR-7, miR-153, miR-152, miR-15B, miR-203 and miR-144 in HEK293T, SH SY5Y and 1321 N1 cells following exposure to ethanol. These miRNAs are predicted to target key genes involved in the pathophysiology of alcoholism. Chronic and chronic-intermittent exposure to ethanol, and its removal, resulted in specific changes in miRNA expression in each cell line suggesting that different expression patterns can be elicited with different exposure paradigms and that the mechanism of ethanol's effects is dependent on cell type. Specifically, chronic exposure to ethanol for five days followed by a five day withdrawal period resulted in up-regulation of several miRNAs in each of these cell lines similar to expression changes identified in post mortem human brain. Thus, this model can be used to elucidate the role of miRNAs in regulating gene expression changes that occur in response to ethanol exposure.

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