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. (ANI)