Brief alcohol exposure alters transcription in astrocytes via the heat shock pathway
Article first published online: 6 FEB 2013
© 2013 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Brain and Behavior
Volume 3, Issue 2, pages 114–133, March 2013
How to Cite
Pignataro, L., Varodayan, F. P., Tannenholz, L. E., Protiva, P. and Harrison, N. L. (2013), Brief alcohol exposure alters transcription in astrocytes via the heat shock pathway. Brain and Behavior, 3: 114–133. doi: 10.1002/brb3.125
- Issue published online: 14 MAR 2013
- Article first published online: 6 FEB 2013
- Manuscript Accepted: 7 JAN 2013
- Manuscript Revised: 23 DEC 2012
- Manuscript Received: 9 JAN 2012
- National Institutes of Health (NIH)/NIAAA. Grant Number: R21 AA018783
- alcohol response element;
- gene expression;
- heat shock factor 1;
Astrocytes are critical for maintaining homeostasis in the central nervous system (CNS), and also participate in the genomic response of the brain to drugs of abuse, including alcohol. In this study, we investigated ethanol regulation of gene expression in astrocytes. A microarray screen revealed that a brief exposure of cortical astrocytes to ethanol increased the expression of a large number of genes. Among the alcohol-responsive genes (ARGs) are glial-specific immune response genes, as well as genes involved in the regulation of transcription, cell proliferation, and differentiation, and genes of the cytoskeleton and extracellular matrix. Genes involved in metabolism were also upregulated by alcohol exposure, including genes associated with oxidoreductase activity, insulin-like growth factor signaling, acetyl-CoA, and lipid metabolism. Previous microarray studies performed on ethanol-treated hepatocyte cultures and mouse liver tissue revealed the induction of almost identical classes of genes to those identified in our microarray experiments, suggesting that alcohol induces similar signaling mechanisms in the brain and liver. We found that acute ethanol exposure activated heat shock factor 1 (HSF1) in astrocytes, as demonstrated by the translocation of this transcription factor to the nucleus and the induction of a family of known HSF1-dependent genes, the heat shock proteins (Hsps). Transfection of a constitutively transcriptionally active Hsf1 construct into astrocytes induced many of the ARGs identified in our microarray study supporting the hypothesis that HSF1 transcriptional activity, as part of the heat shock cascade, may mediate the ethanol induction of these genes. These data indicate that acute ethanol exposure alters gene expression in astrocytes, in part via the activation of HSF1 and the heat shock cascade.