Brain DNA ‘Remodeled’ in Alcoholism
[Writer] This is Research News from U-I-C, the University of Illinois at Chicago.
Dr. Subhash Pandey is Professor and Director of Neuroscience Alcoholism Research in the Department of Psychiatry at the UIC College of Medicine and the Jesse Brown VA Medical Center in Chicago. Today he talks about how reshaping of the DNA scaffolding that supports and controls the expression of genes in the brain may play a major role in alcohol withdrawal symptoms, particularly anxiety.
Here’s Professor Pandey:
[Pandey] The work we are doing over here is looking at the molecular mechanism, in other words the neurochemical basis of alcoholism, and particularly in this piece of work we have done, we have looked at how the alcohol exposure, both single dose as well as longer exposure to alcohol and how it modifies the surrounding where the DNA exists in the neuron, or in the cells in the brain. And what we have found is that, particularly the stem where the DNA exists in the cells and surrounded by the different kinds of proteins, the total assembly known as the nucleosome, consists of the histone and the histone is right by the DNA molecule. What we’ve found for the first time here is that alcohol has the tendency to open the structure, which is chromatin, and make the other transcriptional messenger RNA, the molecules which are required to model gene expression make more accessible to this chromatin structure and therefore there’s more gene expression.
So, in other words, the people may not bond with the abnormality in the sequence in their DNA, but because of the alcohol drinking that opened the chromatin structure that may produce the gene expression, that may lead to the abnormal neural function and ultimately the behavior. And what we found again here is that after long alcohol exposure, there’s a tendency in the brain, the neuroadaptation to the acute alcohol exposure, and things go in the opposite direction. During withdrawal, when the alcohol is out, the chromatin structures are down, which means that the histone where the DNA is wrapped around, there is acetylation.
So, I would like to say here how this chromatin structure opens and closes. This histone molecule, when the acetyl group attaches to this, it opens the chromatin structure. When the acetyl group is removed from the histone, then it closes the chromatin structure. And this is known as, in science terms, epigenetic changes. During withdrawal, the acetyl group goes away. Chromatin structure closes, shuts down the gene expression, and we see the alcohol withdrawal symptoms such as anxiety. Anxiety is a very important withdrawal symptom. It appears at the early stages during withdrawal and it is important because people continue to drink alcohol to self-medicate because alcohol has anti-anxiety properties. So when they drink alcohol, then again the chromatin structure opens, makes more genes and controls the behavior.
Here we used a compound which can open the chromatin structure during withdrawal. And when we gave this compound to the animal model, an animal which is physically dependent to alcohol, and then during withdrawal, this compound opened the chromatin structure and it blocked the withdrawal symptoms. So for the first time we demonstrated that moderating the chromatin structure in the brain you can manipulate or moderate the alcohol withdrawal symptoms. In other words, if you open the chromatin structure during alcohol withdrawal, you can prevent the development of alcohol withdrawal symptoms. So we believe, this enzyme, this inhibitor, this compound, which acts on a very important enzyme which regulates the chromatin modeling, is maybe a future target to cure alcoholism.
[Writer] Dr. Subhash Pandey is Professor and Director of Neuroscience Alcoholism Research in the Department of Psychiatry at the UIC College of Medicine and the Jesse Brown VA Medical Center in Chicago.
For more information about this research, go to www-dot-news-dot- uic-dot-edu … click on “news releases” … and look for the release dated April 2, 2008.
This has been research news from U-I-C – the University of Illinois at Chicago.