Gene editing could combat the predisposition for alcoholism

A study just published in Science Advances by researchers at the University of Illinois, Chicago, argues that acting on a specific region of the brain could decrease the risk of falling into the spiral of alcoholism in adults, and precisely in those who have been abused in age. adolescent binge drinking, an expression used to indicate the intake of many alcoholic beverages in a very short time. Not only that, the same procedure could also decrease the possibility of suffering from serious disorders related to anxiety states.

To do this, the researchers explain, it is necessary to resort to genetic editing, capable of "canceling" a person's predisposition to develop these disorders.

In a previous study, the same team of research had focused on how adolescent binge drinking could affect the brain and have long-lasting effects. Furthermore, it was emphasized that this practice alters the chemistry of a specific region of the brain, and more precisely it reduces the expression of the Arc gene (activity regulated cytoskeletal-associated protein) in the amygdala, the center for the regulation of emotions and memory, both rodents than humans. An epigenetic “reprogramming” of this gene, the team specified, which contributes to a greater predisposition to develop anxiety disorders and alcoholism in adulthood.

In new experiments, for now conducted only on animal models, researchers have tried to understand if these epigenetic reprogramming effects can be "reversed", using a technique called Crispr-dCas9 to manipulate acetylation and methylation processes of the Arc gene. In detail, it was observed in adult rodents previously exposed to alcohol that when dCas9 was used to promote histone acetylation, a process that allows transcription factors to bind to DNA, Arc gene expression normalized. And, as a result, the indicators of anxiety and alcohol consumption decreased. Anxiety, as the researchers say, was measured with behavioral tests, for example by monitoring exploratory activity in a maze, while alcohol consumption was measured by observing the amount of fluid consumed when the rodents were presented with the choice of bottles containing water and different concentrations of alcohol (3%, 7% and 9%).

In a subsequent experiment, the researchers focused on a group of rats that had never been exposed to alcohol. From here, they observed that dCas9, used to promote methylation, a process that prevents transcription factors from binding to DNA, Arc gene expression decreased and indicators of anxiety and alcoholism increased. "These results demonstrate that epigenetic editing in the amygdala can improve the psychopathology of adults after alcohol exposure in adolescence," the authors report. the importance ofa> adolescence as a key period of brain development and how binge drinking throughout this period can increase the risk not only of the disorder related to alcohol abuse, but also of psychiatric disorders, such as anxiety. Research, therefore, not only improves our understanding of the biological mechanisms underlying these relationships, but proposes new possibilities for how these conditions might be treated. "Teenage binge drinking is a serious public health problem and this study not only helps us better understand what happens in a developing brain when exposed to high concentrations of alcohol, but more importantly, it gives us hope that one day we will have effective treatments for complex diseases such as anxiety and alcohol consumption disorder, ”concludes Pandey.