Alcohol‐responsive genes in the frontal cortex and nucleus accumbens of human alcoholics

Flatscher-Bader, Traute; Brug, Marcel van der; Hwang, John W; Gochee, Peter A.; Matsumoto, Izuru; Niwa, Shin‐Ichi; Wilce, Peter A.

doi:10.1111/j.1471-4159.2005.03282.x

Cited by 74 publications

(96 citation statements)

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“…Chronic ethanol treatment of rats results in DNA damage and an increased level of heat shock proteins in the cortex (78,79) . Correspondingly, in the PFC of the human alcoholic, genes associated with DNA repair and those encoding a number of heat shock proteins and free radical scavengers were induced (64,65,69) . The down-regulation of mitochondrial genes including those associated with electron transport or energy production was revealed in two studies (64,67) .…”

Section: Gene Expression Profiling Of the Human Prefrontal Cortex Of mentioning

confidence: 99%

“…Correspondingly, in the PFC of the human alcoholic, genes associated with DNA repair and those encoding a number of heat shock proteins and free radical scavengers were induced (64,65,69) . The down-regulation of mitochondrial genes including those associated with electron transport or energy production was revealed in two studies (64,67) . Mitochondrial function was again implicated in the animal model of alcohol preference (36) .…”

Section: Gene Expression Profiling Of the Human Prefrontal Cortex Of mentioning

confidence: 99%

“…These studies also identified an alteration in the expression of genes concerned with myelination, which may point to an interference of alcohol with membrane integrity and neurotransmission. Further, in two studies the expression of transcription factors, including the immediate early genes, activator protein 1 (AP-1) and CREB, was sensitive to chronic alcohol abuse (64,69) . These results are in accordance with expression profiling in the animal models (36) and may indicate an alteration to cell fate in the PFC of the long-term alcoholic.…”

Section: Gene Expression Profiling Of the Human Prefrontal Cortex Of mentioning

confidence: 99%

“…These studies revealed changes to the expression of several hundred genes in the chronic alcoholic (65,66) , including genes concerned with myelination. Advances in technology later enabled investigators to profile the transcriptome of the PFC in individual samples (64,67,69) . These studies also identified an alteration in the expression of genes concerned with myelination, which may point to an interference of alcohol with membrane integrity and neurotransmission.…”

Section: Gene Expression Profiling Of the Human Prefrontal Cortex Of mentioning

confidence: 99%

“…In a series of microarray studies our research group profiled the PFC (BA 9), NAC and VTA of long-term alcohol abusers (63,64) using a consistent method of RNA extraction, linear amplification, microarray platform, hybridization, as well as data analysis. In the studies of the BA 9 region of the PFC and the NAC a two-colour design was used (64) , while for expression screening of the VTA a universal reference was applied (63) .…”

Section: Comparative Gene Expression Profiling Of Regions Of the Dopamentioning

confidence: 99%

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The effect of alcohol and nicotine abuse on gene expression in the brain

Flatscher-Bader

Wilce

2009

Nutr. Res. Rev.

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Alcohol intake at levels posing an acute heath risk is common amongst teenagers. Alcohol abuse is the second most common mental disorder worldwide. The incidence of smoking is decreasing in the Western world but increasing in developing countries and is the leading cause of preventable death worldwide. Considering the longstanding history of alcohol and tobacco consumption in human societies, it might be surprising that the molecular mechanisms underlying alcohol and smoking dependence are still incompletely understood. Effective treatments against the risk of relapse are lacking. Drugs of abuse exert their effect manipulating the dopaminergic mesocorticolimbic system. In this brain region, alcohol has many potential targets including membranes and several ion channels, while other drugs, for example nicotine, act via specific receptors or binding proteins. Repeated consumption of drugs of abuse mediates adaptive changes within this region, resulting in addiction. The high incidence of alcohol and nicotine co-abuse complicates analysis of the molecular basis of the disease. Gene expression profiling is a useful approach to explore novel drug targets in the brain. Several groups have utilised this technology to reveal drug-sensitive pathways in the mesocorticolimbic system of animal models and in human subjects. These studies are the focus of the present review.

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Section: Gene Expression Profiling Of the Human Prefrontal Cortex Of mentioning

confidence: 99%

Section: Gene Expression Profiling Of the Human Prefrontal Cortex Of mentioning

confidence: 99%

Section: Gene Expression Profiling Of the Human Prefrontal Cortex Of mentioning

confidence: 99%

Section: Gene Expression Profiling Of the Human Prefrontal Cortex Of mentioning

confidence: 99%

Section: Comparative Gene Expression Profiling Of Regions Of the Dopamentioning

confidence: 99%

See 3 more Smart Citations

The effect of alcohol and nicotine abuse on gene expression in the brain

Flatscher-Bader

Wilce

2009

Nutr. Res. Rev.

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Brief alcohol exposure alters transcription in astrocytes via the heat shock pathway

et al. 2013

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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.

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Modeling the Diagnostic Criteria for Alcohol Dependence with Genetic Animal Models

Crabbe

Kendler

Hitzemann

2011

Behavioral Neurobiology of Alcohol Addiction

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A diagnosis of alcohol dependence (AD) using the DSM-IV-R is categorical, based on an individual’s manifestation of three or more symptoms from a list of seven. AD risk can be traced to both genetic and environmental sources. Most genetic studies of AD risk implicitly assume that an AD diagnosis represents a single underlying genetic factor. We recently found that the criteria for an AD diagnosis represent three somewhat distinct genetic paths to individual risk. Specifically, heavy use and tolerance versus withdrawal and continued use despite problems reflected separate genetic factors. However, some data suggest that genetic risk for AD is adequately described with a single underlying genetic risk factor. Rodent animal models for alcohol-related phenotypes typically target discrete aspects of the complex human AD diagnosis. Here, we review the literature derived from genetic animal models in an attempt to determine whether they support a single-factor or multiple-factor genetic structure. We conclude that there is modest support in the animal literature that alcohol tolerance and withdrawal reflect distinct genetic risk factors, in agreement with our human data. We suggest areas where more research could clarify this attempt to align the rodent and human data.

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Alcohol‐responsive genes in the frontal cortex and nucleus accumbens of human alcoholics

Cited by 74 publications

References 1 publication

The effect of alcohol and nicotine abuse on gene expression in the brain

The effect of alcohol and nicotine abuse on gene expression in the brain

Brief alcohol exposure alters transcription in astrocytes via the heat shock pathway

Modeling the Diagnostic Criteria for Alcohol Dependence with Genetic Animal Models

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