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Alcohol‐responsive genes in the frontal cortex and nucleus accumbens of human alcoholics
Author(s) -
FlatscherBader Traute,
van der Brug Marcel,
Hwang John W,
Gochee Peter A,
Matsumoto Izuru,
Niwa Shinichi,
Wilce Peter A
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2004.03021.x
Subject(s) - nucleus accumbens , prefrontal cortex , neuroscience , biology , dorsolateral prefrontal cortex , central nervous system , cognition
The molecular processes underlying alcohol dependence are not fully understood. Many characteristic behaviours result from neuroadaptations in the mesocorticolimbic system. In addition, alcoholism is associated with a distinct neuropathology. To elucidate the molecular basis of these features, we compared the RNA expression profile of the nucleus accumbens and prefrontal cortex of human brain from matched individual alcoholic and control cases using cDNA microarrays. Approximately 6% of genes with a marked alcohol response were common to the two brain regions. Alcohol‐responsive genes were grouped into 11 functional categories. Predominant alcohol‐responsive genes in the prefrontal cortex were those encoding DNA‐binding proteins including transcription factors and repair proteins. There was also a down‐regulation of genes encoding mitochondrial proteins, which could result in disrupted mitochondrial function and energy production leading to oxidative stress. Other alcohol‐responsive genes in the prefrontal cortex were associated with neuroprotection/apoptosis. In contrast, in the nucleus accumbens, alcohol‐responsive genes were associated with vesicle formation and regulation of cell architecture, which suggests a neuroadaptation to chronic alcohol exposure at the level of synaptic structure and function. Our data are in keeping with the previously reported alcoholism‐related pathology characteristic of the prefrontal cortex, but suggest a persistent decrease in neurotransmission and changes in plasticity in the nucleus accumbens of the alcoholic.