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.
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.
Authors: Duonan Yu; Camila O dos Santos; Guowei Zhao; Jing Jiang; Julio D Amigo; Eugene Khandros; Louis C Dore; Yu Yao; Janine D'Souza; Zhe Zhang; Saghi Ghaffari; John Choi; Sherree Friend; Wei Tong; Jordan S Orange; Barry H Paw; Mitchell J Weiss Journal: Genes Dev Date: 2010-08-01 Impact factor: 11.361
Authors: Leonardo Pignataro; Florence P Varodayan; Lindsay E Tannenholz; Neil L Harrison Journal: Pharmacol Ther Date: 2009-09-23 Impact factor: 12.310
Authors: Heidi M B Lesscher; Julia M Houthuijzen; Marian J Groot Koerkamp; Frank C P Holstege; Louk J M J Vanderschuren Journal: PLoS One Date: 2012-05-22 Impact factor: 3.240