Apoptosis and gene expression: perspectives on alcohol-induced brain damage.

Apoptosis, genetically preprogrammed death of scattered cells, leaves few histological traces and is compatible with autopsy findings in brains of alcoholics. This type of cell death could be triggered by chronic exposure to alcohol. Interactions between alcohol and the activating and inhibiting molecular events of the apoptotic cascade could occur at several different levels. Sites of alcohol action could range from the transcription of the apoptosis genes to translation and posttranslational modifications of their protein products. The recent developments of in situ hybridization technology make it possible to determine the levels of the neurotoxic actions of ethanol and to detect early stages of toxicity where increased mRNA activity may compensate for losses of receptors, enzymes, peptide transmitters, or structural proteins. The potential for treatment with antisense nucleotides is discussed.