Dysregulation of Cell Death Machinery in the Prefrontal Cortex of Human Alcoholics

Overview

Journal Int J Neuropsychopharmacol

Publisher Oxford University Press

Specialty Psychiatry

Date 2008 Oct 22

PMID 18937880

Citations 10

Authors

Sofia Johansson

Tomas J Ekstrom

Zoya Marinova

Anna Okvist

Donna Sheedy

Therese Garrick

Clive Harper

Alexander Kuzmin

Tatjana Yakovleva

Georgy Bakalkin

Affiliations

Soon will be listed here.

Abstract

In human alcoholics, the cell density is decreased in the prefrontal cortex (PFC) and other brain areas. This may be due to persistent activation of cell death pathways. To address this hypothesis, we examined the status of cell death machinery in the dorsolateral PFC in alcoholics. Protein and mRNA expression levels of several key pro- and anti-apoptotic genes were compared in post-mortem samples of 14 male human alcoholics and 14 male controls. The findings do not support the hypothesis. On the contrary, they show that several components of intrinsic apoptotic pathway are decreased in alcoholics. No differences were evident in the motor cortex, which is less damaged in alcoholics and was analysed for comparison. Thus, cell death mechanisms may be dysregulated by inhibition of intrinsic apoptotic pathway in the PFC in human alcoholics. This inhibition may reflect molecular adaptations that counteract alcohol neurotoxicity in cells that survive after many years of alcohol exposure and withdrawal.

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