CRISPR tool reverse one big consequence of "teenage" drinking in rats

It will be a long time before this type of epigenetic remodeling is available to regular patients.
Grant Currin
A close-up of DNA.selvanegra / iStock

Binge drinking during adolescence can have serious consequences for the brain — both in humans and rats. One change affects a gene that influences the operation of important parts of the brain. It can lead people who drank as teenagers to be more anxious and more prone to alcohol use disorder in adulthood.

In a study published Wednesday in the peer-reviewed journal Science, a team of researchers describe how they used epigenetic editing to reverse the change. 

“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,” says psychiatrist and epigeneticist Subhash Pandey, who is a co-author on the study.

Researchers turned rats into alcoholics — and then reversed it

The sequence of DNA — the exact ordering of A, T, C, and G — isn't the whole story. The way DNA is wrapped up can also affect the cells, leading to dramatic changes. Binge drinking during adolescence, for instance, can impair normal brain development by turning down the ARC gene. ("ARC" is short for activity-regulated cytoskeleton-associated protein immediate-early.) That can change how a part of the brain called the amygdala develops. 

The researchers behind the new study gave a group of four- to six-week-old rats (roughly equivalent to 10- to 18-year-old humans) access to alcohol in a simulation of teenage binge drinking. In some of the rats, they used a gene-editing tool called CRISPR-dCas9 to physically manipulate the DNA  in an attempt to reverse the changes caused by the drinking. Then they put their subjects to the test. The rats that had undergone "epigenetic remodeling" were better at mazes and less inclined to drink alcohol than rats that didn't receive any treatment at all.

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A future for humans?

This study advances the science around alcohol abuse in a couple of ways. First, it confirms the relationship between teenage bingeing and the ARC gene. It also provided evidence of a fix, though it will probably be a long time before such treatment is available for humans. The study "helps us better understand what happens in developing brains when they are exposed to high concentrations of alcohol," Pandey says. [M]ore importantly [it] gives us hope that one day we will have effective treatments for the complex and multifaceted diseases of anxiety and alcohol use disorder," he says.

In a related piece published alongside the research paper, neuroscientists Collin Teague and Eric Nestler caution that it will take a lot of interdisciplinary cooperation to translate this mouse research into a therapy for humans. “Nonetheless, this study represents an important step forward in understanding how alcohol consumption during adolescence predisposes individuals to developing neuropsychiatric disorders later in life," they write. 

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