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.
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 behaviors during withdrawal in animals with chronic alcohol exposure was associated with an increase in HDAC activity and decrease in histones acetylation and NPY levels.
Importantly, blocking the observed increase in HDAC activity using an HDAC inhibitor during alcohol withdrawal brought up histone acetylation and NPY expression levels in the amygdala and prevented the development of anxiety-like behaviors.
"Our findings suggest that HDAC inhibitors may have potential as therapeutic agents in treating alcoholism," Pandey said.
The researchers also found that levels of a protein known as CREB binding protein, which has HAT enzymatic activity, were increased by acute alcohol but were decreased during ethanol withdrawal.
They concluded that the enzymes that are involved in remodeling 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," Pandey said. "Anxiety associated with withdrawal from alcohol abuse is a key factor in the maintenance of alcohol addiction."
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.
The research was supported by grants from the National Institute on Alcohol Abuse and Alcoholism and the Department of Veteran Affairs. Rajesh Ugale, Huaibo Zhang, Lei Tang and Anand Prakash of UIC and the Jesse Brown VA Medical Center also contributed to the study.
- PHYSICAL SCIENCES
- EARTH SCIENCES
- LIFE SCIENCES
- SOCIAL SCIENCES
Subscribe to the newsletter
Stay in touch with the scientific world!
Know Science And Want To Write?
- How Gut Bacteria Ensure A Healthy Brain – and Could Play A Role In Treating Depression
- Researchers Created A Laser Bullet To See What It Would Look Like - And Here It Is
- We're Too Late To Prevent 137,000 More Ebola Cases, Says Epidemiology Paper
- The Strange Organic Molecules In Titan's Atmosphere
- The Quote Of The Week - Shocked And Disappointed
- As Seen on TV: Advertising’s Influence on Alcohol Abuse
- Type 1 Diabetes Surges In White Kids
- "For background, look at Paul Bloom’s 2004 book Descartes’ Baby. This has interesting material..."
- " It is possible that survival of Ebola virus victims would be much improved if an artificial fever..."
- "Priceless! I really needed a kick in the pants to get me to laugh at myself and this post did it..."
- "You have done an immense amount of work. It would help if you added some boxes to explain how you..."
- "2) All that is possible is possible; none of the impossible will be made possible. 3) None of the..."
- US Ebola hysteria and money pit highlight lack of resources to confront diseases that kill far more people
- Addiction can be measured by epigenetics
- Coffee grounds turned biofuel can heat your home
- Bill and Melinda Gates on GMOs: ‘Poor farmers should not be denied choice of life-saving tools’
- Why do foodies love organics? Because they taste like McDonald’s!
- GMO milk? An enviros dream innovation that most enviros oppose
- Global boom in hydropower expected this decade
- For brain hemorrhage, risk of death is lower at high-volume hospitals
- Roman-Britons had less gum disease than modern Britons
- 'Swingers' multiple drug use heightens risk of sexually transmitted diseases
- Were clinical trial practices in East Germany questionable?