NEW YORK (Dec. 7, 2007) -- Alcohol triggers the activation of a variety of genes that can influence the health and activity of brain cells, and new research from Weill Cornell Medical College in New York City sheds light on how that process occurs.
The findings, published in the Nov. 21 issue of The Journal of Neuroscience, may also edge scientists closer to understanding alcohol-linked disorders such as the brain damage associated with chronic alcoholism, and the abnormal brain development seen in the fetal alcohol syndrome (FAS).
"If you are going to understand the biological effects of alcohol on genes within cells, you have to understand the molecular machinery driving the transcription, or activation, of the genes in question. That's what we believe we have done here," says the study's senior author Dr. Neil L. Harrison, professor of pharmacology and pharmacology in anesthesiology at Weill Cornell.
In research conducted in cell cultures and in mouse neurons in vivo, his team found that alcohol stimulates a ubiquitous, stress-linked biochemical cascade -- called the heat shock pathway -- to send a molecule called heat shock factor 1 (HSF1) into the neuron's nucleus. HSF1 then stimulates the transcription of many of the genes known to be activated by alcohol.
The fact that alcohol triggers the activation of genes in the brain is not new and has long been the subject of intense research.
One gene in particular, called Gabra4, is closely linked to the function (or dysfunction) of receptors for GABA, an important neurotransmitter.
"We knew that levels of expression of Gabra4 fluctuated rapidly in the presence of alcohol, and so we wondered if we could find out how this happens," says lead author Dr. Leonardo Pignataro, instructor in pharmacology in anesthesiology at Weill Cornell.
At the same time, research in Korea with the C. elegans worm (a common tool for genomics research) had discovered t
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New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College