Study Sheds Light on How Alcohol Affects Brain Cells

A new research has shed light on how alcohol triggers the activation of a number of genes that can influence the health and activity of brain cells.

Researchers at the Weill Cornell Medical College in New York City conducted the study in cell cultures and in mouse neurons in vivo, and 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 authors say that the findings 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," said the study's senior author Dr. Neil L. Harrison, professor of pharmacology and pharmacology in anesthesiology at Weill Cornell.

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," said lead author Dr. Leonardo Pignataro, instructor in pharmacology in anesthesiology at Weill Cornell.

Working with mouse cells in the lab, the researchers used microarray technologies to search for genes other than Gabra4 that might be activated when the heat shock pathway was exposed to alcohol. They found many others.

"The big question that remains is how does this activation occur? The current theory holds that, under conditions of stress, heat shock proteins break away from a key molecule, HSF1. HSF1 then makes its way to the cell nucleus, where it helps stimulate the transcription and activation of a variety of genes that enable the cell to survive stress. We think this may happen with alcohol exposure," Dr. Harrison said.

This finding, observed in vitro in the cell cultures, was replicated in vivo experiments in mice, conducted in the lab of Dr. Daniel Herrera, assistant professor of psychiatry at Weill Cornell.

The researchers, however, stress that the exact meaning and significance of those effects clinically remains in the realm of speculation for now.

"Alcohol can have bad effects—the well-known effects of alcoholism, such as liver or brain damage, for example—but moderate alcohol use also has more benign effects, such as the improvement in cardiovascular health observed in drinkers of red wine compared with tee-totallers," Dr. Pignataro said.

The study is published in the Nov. 21 issue of The Journal of Neuroscience.

Source-ANI
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