CRISPR can reverse epigenetic changes caused by adolescent binge drinking

A 'factory reset' of the brain, using genome editing, could be used to treat alcohol addiction and anxiety, scientists have suggested.

The team, from the University of Illinois Chicago (UIC), had previously linked binge drinking in adolescence to long term alterations in epigenetic programming at the Arc gene, resulting in a decrease in Arc expression in the amygdala of rodents and humans. The amygdala is a part of the brain that helps define and regulate emotions, and these epigenetic changes result in a predisposition to anxiety and alcohol use disorder in adulthood. In the current study, the researchers showed that this epigenetic reprogramming induced by adolescent alcohol exposure can be reversed using genome editing.

'Early binge drinking can have long-lasting and significant effects on the brain and the results of this study offer evidence that genome editing is a potential antidote to these effects,' said senior author Professor Subhash Pandey, a professor of psychiatry and director of the Centre for Alcohol Research in Epigenetics at UIC. He also stated that this technique could 'offer a kind of factory reset for the brain, if you will.'

The team, who published their results in Science Advances, first exposed rats to binge drinking at a time in their development coinciding with human adolescence. Anxiety was measured by exploratory activity of rats in maze tests and preference for alcohol was measured by monitoring the amount of liquid consumed when the rats were presented with a choice of two bottles consisting of options such as tap water, sugar water and varying concentrations of alcohol.

The scientists used the CRISPR-dCas9 genome editing approach to manipulate the histone acetylation and methylation processes at the Arc gene, which are known epigenetic modifications.

The study found that when dCas9 was used to promote histone acetylation in adult rats exposed to alcohol during adolescence, Arc gene expression returned to normal, and the subsequent increase in ARC protein levels led to a reduction in anxiety and alcohol drinking.

In contrast, when dCas9 was used to promote histone methylation in adult rats not exposed to alcohol during adolescence, Arc gene expression decreased leading to an increase in anxiety and alcohol drinking.

These results demonstrate that epigenomic editing to the Arc gene in the amygdala can improve adult anxiety and alcohol dependence after alcohol exposure as an adolescent.

'Adolescent binge drinking is a serious public health issue, and this study not only helps us better understand what happens in developing brains when they are exposed to high concentrations of alcohol but more importantly gives us hope that one day we will have effective treatments for the complex and multifaceted diseases of anxiety and alcohol use disorder,' said Professor Pandey.

The authors also note that, while these data suggest that epigenomic editing at Arc can bidirectionally modulate behavioural changes caused by adolescent alcohol exposure, further studies are needed.