Differential Expression of 14-3-3 Isoforms in Human Alcoholic Brain

Abstract

Keywords: Alcohol Abuse; Gene Expression; Ethanol; Real-Time PCR Background: Neuropathological damage as a result of chronic alcohol abuse often results in the impairment of cognitive function. The damage is particularly marked in the frontal cortex. The 14-3-3 protein family consists of 7 proteins, ߬ ?, e, ?, ?, ?, and s, encoded by 7 distinct genes. They are highly conserved molecular chaperones with roles in the regulation of metabolism, signal transduction, cell-cycle control, protein trafficking, and apoptosis. They may also play an important role in neurodegeneration in chronic alcoholism. Methods: We used real-time PCR to measure the expression of 14-3-3 mRNA transcripts in both the dorsolateral prefrontal cortex and motor cortex of human brains obtained at autopsy. Results: We found significantly lower 14-3-3߬ ?, and ? expression in both cortical areas of alcoholics, but no difference in 14-3-3? expression, and higher expression of 14-3-3s in both areas. Levels of 14-3-3? and e transcripts were significantly lower only in alcoholic motor cortex. Conclusions: Altered 14-3-3 expression could contribute to synaptic dysfunction and altered neurotransmission in chronic alcohol misuse by human subjects