Exon Microarray Analysis of Human Dorsolateral Prefrontal Cortex in Alcoholism. (30th May 2014)

• Record Type: Journal Article
• Authors: Manzardo, Ann M.; Gunewardena, Sumedha; Wang, Kun; Butler, Merlin G.
• Is Part Of: Alcoholism. Volume 38:Number 6(2014:Jun.)
• Page Start: 1594
• Page End: 1601
• Publication Date: 2014-05-30
• Subjects: Alcoholism -- Periodicals; Alcoholism -- Periodicals; Alcoolisme; Electronic journals; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.861005
• DOI: 10.1111/acer.12429
• Languages: English
• ISSNs: 0145-6008

Abstract

<abstract abstract-type="main" id="acer12429-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="acer12429-sec-0001" sec-type="section"> <title>Background</title> <p>Alcohol abuse is associated with cellular and biochemical disturbances that impact upon protein and nucleic acid synthesis, brain development, function, and behavioral responses. To further characterize the genetic influences in alcoholism and the effects of alcohol consumption on gene expression, we used a highly sensitive exon microarray to examine mRNA expression in human frontal cortex of alcoholics and control males.</p> </sec> <sec id="acer12429-sec-0002" sec-type="section"> <title>Methods</title> <p>Messenger RNA was isolated from the dorsolateral prefrontal cortex (dlPFC; Brodmann area 9) of 7 adult alcoholic (6 males, 1 female, mean age 49 years) and 7 matched controls. Affymetrix Human Exon 1.0 ST array was performed according to standard procedures and the results analyzed at the gene level. Microarray findings were validated using quantitative reverse transcription polymerase chain reaction, and the ontology of disturbed genes characterized using Ingenuity Pathway Analysis (IPA).</p> </sec> <sec id="acer12429-sec-0003" sec-type="section"> <title>Results</title> <p>Decreased mRNA expression was observed for genes involved in cellular adhesion (e.g., <italic>CTNNA3</italic>, <italic>ITGA2</italic>), transport (e.g., <italic>TF</italic>, <italic>ABCA8</italic>), nervous system development (e.g., <italic>LRP2</italic>, <italic>UGT8</italic>, <italic>GLDN</italic>), and signaling (e.g., <italic>RASGRP3</italic>, <italic>LGR5</italic>) with influence over lipid and myelin synthesis (e.g., <italic>ASPA</italic>, <italic>ENPP2</italic>, <italic>KLK6</italic>). IPA identified disturbances in network functions associated with neurological disease and development including cellular assembly and organization impacting on psychological disorders.</p> </sec> <sec id="acer12429-sec-0004" sec-type="section"> <title>Conclusions</title> <p>Our data in alcoholism support a reduction in expression of dlPFC mRNA for genes involved with neuronal growth, differentiation, and signaling that targets white matter of the brain.</p> </sec> </abstract>