An intriguing new study focuses on a region of the brain that is central to the development of both alcohol abuse and adult anxiety, and demonstrates how gene editing can be used to address a person’s predisposition to both diseases. Compared to the “factory reset” of the brain, the technique has been proposed as a potential way to treat conditions that can be traced back to adolescence, and offers new insights into the effects on brain health from excessive drinking at a young age.

The study was conducted by researchers at the University of Illinois at Chicago and is based on previous work examining ways in which drinking during adolescence can alter brain chemistry with long-term effects. Scientists have previously found that excessive drinking during these years of formation reduces the expression of the activity-regulated cytoskeleton protein (Arc) protein in the amygdala, a brain region that is a key center for emotion regulation.

One of the lasting effects of this epigenetic reprogramming of the Arc gene, scientists have found, is an increased susceptibility to anxiety and disorders in alcohol use in adulthood. For their new study, the researchers tried to investigate whether these effects could be reversed using modern gene editing techniques, namely CRISPR-d ​​Cas9.

In their experiments, rats were subjected to periodic exposure to alcohol during adolescence, corresponding to ages 10 to 18 in humans. When the rats reached adulthood, the researchers used CRISPR-d ​​Cas9 to normalize Arc gene expression, which in turn reduced anxiety and preference for alcohol consumption.

They were measured by behavioral tests and labyrinth experiments to measure rodent anxiety levels and experiments that presented them with a choice of different liquids containing different concentrations of alcohol. Inverse experiments have shown that the use of CRISPR-d ​​Cas9 to reduce Arc gene expression has the opposite effect, increasing anxiety and preference for alcohol consumption.

“Early 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 resetting of the brain if desired,” said study author Subhash Pandey.

In their study, the researchers emphasized the importance of adolescence as a key period in brain development and how excessive drinking all the time can increase the risk of more than just alcoholism, which is leading cause of preventable deathbut psychiatric disorders such as anxiety. The study not only sheds new light on the biological mechanisms underlying these relationships, but raises some interesting new possibilities for how these conditions can be treated.

“Adolescent binge drinking is a serious public health problem, and this study not only helps us better understand what happens in developing brains when they are exposed to high levels of alcohol, but more importantly, it gives us hope that “One day we will have effective treatments for complex and multifaceted anxiety disorders and alcohol-related disorders,” Pandi said. “The fact that this effect is observed in two directions confirms the importance of the gene for amplifying the rainbow in the amygdala in the epigenetic reprogramming of adolescent drinking.

The study was published in the journal science.

Source: University of Illinois at Chicago

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