Reshaping of the DNA scaffolding that supports and controls the expression of genes in the brain may play a major role in the alcohol withdrawal symptoms, particularly anxiety, that make it so difficult for alcoholics to stop using alcohol.
The finding is reported by researchers at the University of Illinois at Chicago and the Jesse Brown VA Medical Center in the April 2 issue of the Journal of Neuroscience.
DNA can undergo changes in function without any changes in inheritance or coded sequence. 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 remodeling in the brain during alcohol addiction," said 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, the lead author of the study.
Chemical modification of histones can change the way DNA and histones are wound up together. Histone acetyltransferases (HATs) are enzymes that add acetyl groups to histones and loosen the packing, promoting gene expression. On the other hand, histone deacetylases (HDACs) remove acetyl groups from histones, causing them to wrap with DNA more tightly, decreasing gene expression.
The UIC researchers had previously shown in an animal model that levels of neuropeptide Y in the amygdala modulate anxiety and alcohol-drinking behavior. In the new study, they looked at the HDAC activity, acetylation of histones, and expression of the genes for NPY in the amygdala and the anxiety-like behaviors associated with withdrawal from chronic alcohol use.
Pandey and his colleagues found that acute exposure to alcohol decreases HDAC activity; increases the acetylation histones; increases levels of NPY -- and reduced anxiety in the animals.
Conversely, anxiety-like behavio
|Contact: Jeanne Galatzer-Levy|
University of Illinois at Chicago