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, β, γ, ε, ζ, η, θ, and σ, 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 14-3-3β, γ, and θ expression in both cortical areas of alcoholics, but no difference in 14-3-3η expression, and higher expression of 14-3-3σ in both areas. Levels of 14-3-3ζ and ε 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