More than 100 million people worldwide are dependent on alcohol. To date, there is little that can be done medicinally to combat the disease. In addition, the recurrence rate is extremely high at up to 90 percent. Researchers led by Subhash Pandey from the University of Illinois in Chicago have now discovered a molecular mechanism in rats that could pave the way for more efficient therapy for alcoholism, as they report in “Science Advances”.
Excessive drinking (binge drinking) in youth is one of the risk factors for alcohol dependence in adulthood, but also for anxiety disorders. During puberty, the brain is undergoing restructuring and is very sensitive to environmental influences. The so-called Arcgene is of particular importance: Not only does it play a central role in synaptic plasticity, it is also epigenetically modified under the influence of early alcohol consumption. Epigenetic modifications are reversible chemical changes in the DNA or histones that package the genome.
Depending on whether the DNA is compressed or loosened as a result, certain genes can be read better or worse or translated into proteins. Young rats that were given a lot of alcohol to drink had less of the Arc protein in the amygdala, a region involved in both alcohol addiction and the regulation of anxiety, according to previous research by the group. Pandey and his colleagues found the same thing in brain sections of deceased alcoholic people.
In the current study, the team wanted to find out whether these changes can be reversed – the epigenetic switch can be flipped, so to speak. To do this, it used the CRISPR-Cas gene scissors, which can be used to change the histone packaging of the DNA in both directions. In one of their experiments, the researchers repeatedly administered large amounts of alcohol to young rats between the ages of 27 and 41 (equivalent to 10 to 18 years of age in humans). They later used gene scissors on the adult, now alcoholic, animals in such a way that Arc production was boosted again. They then tested how often the rats drank water instead of alcohol and how anxious they were.