Chronic Alcohol Exposure and the Circadian Clock Mutation Exert Tissue‐Specific Effects on Gene Expression in Mouse Hippocampus, Liver, and Proximal Colon. (2nd September 2015)

• Record Type: Journal Article
• Authors: Summa, Keith C.; Jiang, Peng; Fitzpatrick, Karrie; Voigt, Robin M.; Bowers, Samuel J.; Forsyth, Christopher B.; Vitaterna, Martha H.; Keshavarzian, Ali; Turek, Fred W.
• Is Part Of: Alcoholism. Volume 39:Number 10(2015:Oct.)
• Page Start: 1917
• Page End: 1929
• Publication Date: 2015-09-02
• Subjects: Alcoholism -- Periodicals; Alcoholism -- Periodicals; Alcoolisme; Electronic journals; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.861005
• DOI: 10.1111/acer.12834
• Languages: English
• ISSNs: 0145-6008

Abstract

<abstract abstract-type="main" id="acer12834-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="acer12834-sec-0001" sec-type="section"> <title>Background</title> <p>Chronic alcohol exposure exerts numerous adverse effects, although the specific mechanisms underlying these negative effects on different tissues are not completely understood. Alcohol also affects core properties of the circadian clock system, and it has been shown that disruption of circadian rhythms confers vulnerability to alcohol‐induced pathology of the gastrointestinal barrier and liver. Despite these findings, little is known of the molecular interactions between alcohol and the circadian clock system, especially regarding implications for tissue‐specific susceptibility to alcohol pathologies. The aim of this study was to identify changes in expression of genes relevant to alcohol pathologies and circadian clock function in different tissues in response to chronic alcohol intake.</p> </sec> <sec id="acer12834-sec-0002" sec-type="section"> <title>Methods</title> <p>Wild‐type and circadian <italic>Clock</italic><sup><italic>Δ19</italic></sup> mutant mice were subjected to a 10‐week chronic alcohol protocol, after which hippocampal, liver, and proximal colon tissues were harvested for gene expression analysis using a custom‐designed multiplex magnetic bead hybridization assay that provided quantitative assessment of 80 mRNA targets of interest, including 5 housekeeping genes and a predetermined set of 75 genes relevant for alcohol pathology and circadian clock function.</p> </sec> <sec id="acer12834-sec-0003" sec-type="section"> <title>Results</title> <p>Significant alterations in expression levels attributable to genotype, alcohol, and/or a genotype by alcohol interaction were observed in all 3 tissues, with distinct patterns of expression changes observed in each. Of particular interest was the finding that a high proportion of genes involved in inflammation and metabolism on the array was significantly affected by alcohol and the <italic>Clock</italic><sup><italic>Δ19</italic></sup> mutation in the hippocampus, suggesting a suite of molecular changes that may contribute to pathological change.</p> </sec> <sec id="acer12834-sec-0004" sec-type="section"> <title>Conclusions</title> <p>These results reveal the tissue‐specific nature of gene expression responses to chronic alcohol exposure and the <italic>Clock</italic><sup><italic>Δ19</italic></sup> mutation and identify specific expression profiles that may contribute to tissue‐specific vulnerability to alcohol‐induced injury in the brain, colon, and liver.</p> </sec> </abstract>