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"Factory reset" for the brain rewrites risk of anxiety and alcohol abuse

By Nick Lavars 4-4 minutes 5/6/2022

An intriguing new study has zeroed in on a brain region that is central to the development of both alcohol abuse and anxiety in adults, and demonstrated how gene editing could be used to wipe clean a person's predisposition to both disorders. Likened to a "factory reset" for the brain, the technique is put forward as a potential way to treat conditions that can be traced back to adolescence, and offers new insights into the effects on brain health of binge drinking at a young age.

The study was carried out by scientists at the University of Illinois Chicago and builds on previous work exploring the ways binge drinking during adolescence can reshape brain chemistry, with long-lasting effects. The scientists had previously found that binge drinking during those formative years decreases expression of the activity regulated cytoskeleton associated protein (Arc) gene in the amygdala, a brain region that is a key hub for regulating emotions.

One of the lingering effects of this epigenetic reprogramming of the Arc gene, the scientists found, was an increased predisposition to anxiety and alcohol use disorders in adulthood. For their new study, the scientists sought to investigate whether these effects could be reversed with the help of modern gene-editing techniques, namely CRISPR-d Cas9.

In their experiments, rats were subjected to intermittent alcohol exposure during adolescence, corresponding with ages 10 to 18 in humans. When the rats reached adulthood, the scientists used CRISPR-d Cas9 to normalize expression of the Arc gene, which in turn decreased indicators of anxiety and a preference for alcohol consumption.

These were measured through behavioral testing and maze experiments to gauge the rodents' anxiety levels, and experiments that presented them with choices of different liquids containing different concentrations of alcohol. Reverse experiments showed that using CRISPR-d Cas9 to decrease expression of the Arc gene had the opposite effect, boosting indicators of anxiety and a preference for alcohol consumption.

“Early binge drinking can have long-lasting and significant effects on the brain and the results of this study offer evidence that gene editing is a potential antidote to these effects, offering a kind of factory reset for the brain, if you will,” said study senior author Subhash Pandey.

In their study, the scientists emphasize the importance of adolescence as a key period of brain development and how binge drinking throughout it can drive up our risk of not just alcohol use disorder, which is a leading cause of preventable death, but psychiatric disorders like anxiety. The research not only sheds new light on the biological mechanisms underlying these relationships, but raises some interesting new possibilities around how these conditions might be treated.

“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 Pandey. “That this effect was seen bidirectionally validates the significance of the Arc enhancer gene in the amygdala in epigenetic reprogramming from adolescent binge drinking.”

The research was published in the journal Science

Source: University of Illinois Chicago