Washington, April 3 : An Indian-origin researcher in the US has for the first time shown that minor chemical modifications in the brain during alcohol addiction may cause the DNA to undergo changes in function without any changes in inheritance or coded sequence.
Dr. Subhash C. Pandey, professor and director of neuroscience alcoholism research at the UIC College of Medicine and the Jesse Brown VA Medical Center in Chicago, says that these "epigenetic" changes are minor chemical modifications of chromatin, dense bundles of DNA and proteins called histones.
"This is the first time anyone has looked for epigenetic changes related to chromatin remodelling in the brain during alcohol addiction," said Dr. Pandey, the lead author of the study reported in the Journal of Neuroscience.
Dr. Pandey and his colleagues studied the activity of histone deacetylases (HDAC) that remove acetyl groups from histones and, thereby, cause them to wrap with DNA more tightly, decreasing gene expression.
The researchers also looked at the expression of the genes for NPY in the amygdala, and the anxiety-like behaviours associated with withdrawal from chronic alcohol use.
They found that anxiety-like behaviours during withdrawal in animals with chronic alcohol exposure was associated with an increase in HDAC activity and decrease in histones acetylation and NPY levels.
When the researchers blocked the observed increase in HDAC activity using an HDAC inhibitor during alcohol withdrawal, it brought up histone acetylation and NPY expression levels in the amygdala and, thus, prevented the development of anxiety-like behaviours.
"Our findings suggest that HDAC inhibitors may have potential as therapeutic agents in treating alcoholism," Dr. Pandey said.
His team also observed that levels of a protein, called CREB binding protein, which has HAT enzymatic activity, were increased by acute alcohol, but were decreased during ethanol withdrawal.
Based on their observations, the researchers came to the conclusion that the enzymes that are involved in remodelling of chromatin play an important role in the anxiety that accompanies alcohol withdrawal as well as in the anti-anxiety effects of acute alcohol use.
"We need new strategies to treat alcoholism that are directed toward the prevention of withdrawal symptoms. Anxiety associated with withdrawal from alcohol abuse is a key factor in the maintenance of alcohol addiction," Dr. Pandey said.