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|Titolo:||Glutathione-S-transferase expression in the brain: possible role in ethanol preference and longevity|
|Autori interni:||UBALDI, Massimo|
|Data di pubblicazione:||2006|
|Abstract:||Identification of genes that are differentially expressed in rats bidirectionally selected for alcohol preference might reveal biological mechanisms underlying alcoholism or related phenotypes. Microarray analysis from medial prefrontal cortex (mPFC), a key brain region for drug reward, indicated increased expression of glutathione-S-transferases of the alpha (Gsta4) and mu (Gstm1–5) classes in ethanol-preferring AA rats compared with nonpreferring ANA rats. Real-time RT polymerase chain reaction (RT-PCR) analysis demonstrated _ 2-fold higher Gsta4 transcript levels in several brain regions of ethanol-naive AA compared with ANA rats. Differences in mRNA levels were accompanied by differential levels of GSTA4 protein. We identified a novel haplotype variant in the rat Gsta4 gene, defined here as var3. Allele frequencies of var3 were markedly different between AA and ANA rats, 52% and 100%, respectively. Gsta4 expression was strongly correlated with the gene dose of var3, with _ 60% of the variance in expression accounted for by genotype at this locus. The contribution of glutathione S-transferase expression to the ethanol-preferring phenotype is presently unclear. It could, however, underlie observed differences in life span between AA and ANA lines, prompting a utility of this animal model in aging research.|
|Appare nelle tipologie:||Articolo|
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