BACKGROUND: Changes in brain gene expression are thought to be responsible for the tolerance, dependence, and neurotoxicity produced by chronic alcohol abuse, but there has been no large scale study of gene expression in human alcoholism. METHODS: RNA was extracted from postmortem samples of superior frontal cortex of alcoholics and nonalcoholics. Relative levels of RNA were determined by array techniques. We used both cDNA and oligonucleotide microarrays to provide coverage of a large number of genes and to allow cross-validation for those genes represented on both types of arrays. RESULTS: Expression levels were determined for over 4000 genes and 163 of these were found to differ by 40% or more between alcoholics and nonalcoholics. Analysis of these changes revealed a selective reprogramming of gene expression in this brain region, particularly for myelin-related genes which were down-regulated in the alcoholic samples. In addition, cell cycle genes and several neuronal genes were changed in expression. CONCLUSIONS: These gene expression changes suggest a mechanism for the loss of cerebral white matter in alcoholics as well as alterations that may lead to the neurotoxic actions of ethanol.
BACKGROUND: Changes in brain gene expression are thought to be responsible for the tolerance, dependence, and neurotoxicity produced by chronic alcohol abuse, but there has been no large scale study of gene expression in human alcoholism. METHODS: RNA was extracted from postmortem samples of superior frontal cortex of alcoholics and nonalcoholics. Relative levels of RNA were determined by array techniques. We used both cDNA and oligonucleotide microarrays to provide coverage of a large number of genes and to allow cross-validation for those genes represented on both types of arrays. RESULTS: Expression levels were determined for over 4000 genes and 163 of these were found to differ by 40% or more between alcoholics and nonalcoholics. Analysis of these changes revealed a selective reprogramming of gene expression in this brain region, particularly for myelin-related genes which were down-regulated in the alcoholic samples. In addition, cell cycle genes and several neuronal genes were changed in expression. CONCLUSIONS: These gene expression changes suggest a mechanism for the loss of cerebral white matter in alcoholics as well as alterations that may lead to the neurotoxic actions of ethanol.
Authors: E Lehrmann; J Oyler; M P Vawter; T M Hyde; B Kolachana; J E Kleinman; M A Huestis; K G Becker; W J Freed Journal: Pharmacogenomics J Date: 2003 Impact factor: 3.550
Authors: Chella Kamarajan; Bernice Porjesz; Kevin A Jones; Keewhan Choi; David B Chorlian; Ajayan Padmanabhapillai; Madhavi Rangaswamy; Arthur T Stimus; Henri Begleiter Journal: Int J Psychophysiol Date: 2004-01 Impact factor: 2.997
Authors: Charles V Mobbs; Kelvin Yen; Jason Mastaitis; Ha Nguyen; Elizabeth Watson; Elisa Wurmbach; Stuart C Sealfon; Andrew Brooks; Stephen R J Salton Journal: Neurochem Res Date: 2004-06 Impact factor: 3.996
Authors: William J McBride; Mark W Kimpel; Jonathan A Schultz; Jeanette N McClintick; Howard J Edenberg; Richard L Bell Journal: Alcohol Date: 2010-01-29 Impact factor: 2.405
Authors: José Javier Miguel-Hidalgo; Robert Waltzer; Angela A Whittom; Mark C Austin; Grazyna Rajkowska; Craig A Stockmeier Journal: J Affect Disord Date: 2010-06-26 Impact factor: 4.839
Authors: Yuri A Blednov; Susan E Bergeson; Danielle Walker; Vania M M Ferreira; William A Kuziel; R Adron Harris Journal: Behav Brain Res Date: 2005-08-18 Impact factor: 3.332