Alcohol-addicted Rat Brains receive a "factory reset" in gene editing

Alcohol-addicted Rat Brains receive a "factory reset" in gene editing ...

According to an animal research published in Science Advances, gene editing might be a useful therapy for anxiety and alcohol use disorders in adults who were exposed to binge drinking during their adolescence.

Researchers at the University of Illinois Chicago have developed a research into the effects of early life binge drinking on health later in life.

Binge drinking in early childhood alters brain chemistry at the enhancer region of the Arc gene for activity-regulated cytoskeleton-associated protein immediate-early gene, and increases Arc expression in rodents and humans. This epigenetic reprogramming of the Arc gene in the brains emotion and memory center leads to a predisposition to anxiety and alcohol use disorder in adulthood.

The researchers demonstrate that gene editing is effective to reverse this epigenetic reprogramming, which continues throughout life.

According to the study senior author, early binge drinking may have long-lasting and long-term effects on the brain; the findings of this study provide evidence that gene editing is a feasible antidote to these effects, offering a tip of factory reset for the brain if you will, according to the study.

In their experiments, Pandey and his team used a gene-editing technique called CRISPR-dCas9 to modify the histone acetylation and methylation processes at the Arc gene in rats. These processes make genes more or less accessible for activation.

First, researchers studied adult rats with intermittent alcohol exposure in their adolescence, corresponding to about 10 to 18 years old. They found that when dCas9 was used to promote acetylation, an exercise that loosens chromatin and allows transcription factors to bind to the DNA, gene expression normalized. And, indications of anxiety and alcohol consumption decreased.

Anxiety was measured through behavioral testing, such as by documenting the exploratory activity of rats placed in maze tests, and preference for alcohol was measured by monitoring the amount of liquid consumed when rats were presented with a choice of two bottles, which included options, such as tap water, sugar water, and variable concentrations of alcohol (3%, 7%, and 9%).

Adult rats were tested without early alcohol exposure in a second dosage. When inhibitory dCas9 was used to promote methylation, which tightens chromatin and prevents transcription factors from binding to DNA, Arc expression decreased, and markers of anxiety and alcohol consumption increased.

According to the authors, epigenomic analysis in the amygdala is able to help with adult psychopathology following adolescent alcohol exposure.

Adolescent binge drinking is a serious public health problem, and this study improves the ability to understand what happens in developing brains when they are exposed to high concentrations of alcohol, but also gives us hope that one day we will have effective treatments for the complex and multifaceted diseases of anxiety and alcohol use disorder.

According to John Peyton Bohnsack, Huaibo Zhang, Gabriela Wandling, Donghong He, Evan Kyzar, and Amy Lasek, the co-authors of the study, the Targeted epigenomic editing, relieves adult anxiety and excessive drinking following adolescent alcohol exposure.

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