According to the results of an animal study published in the journal, gene editing may be a potential treatment for anxiety and alcohol use disorders in adults exposed to binge drinking in adolescence. scientific progress†
The study was conducted by researchers at the University of Illinois Chicago, who studied the effects of binge drinking early in life on health later in life.
In previous research, the UIC team found that binge drinking in adolescence alters brain chemistry in the enhancer region of the Arc gene — for activity-regulated cytoskeleton-associated protein immediate-early gene — and Arc expression in the amygdala of both rodents and mammals. people decrease. This epigenetic reprogramming of the Arc gene in the emotion and memory center of the brain contributes to a predisposition to anxiety and alcohol use disorders in adulthood.
In the new study, the researchers show that this epigenetic reprogramming, which persists throughout life, can actually be reversed with gene editing.
“Early drinking can have long-lasting and significant effects on the brain, and the results of this study provide evidence that gene editing is a potential antidote to these effects, providing a sort of factory reset for the brain, if you will,” said senior author Subhash Pandey, the Joseph A. Flaherty Endowed Professor of Psychiatry and Director of the Center for Alcohol Research in Epigenetics at UIC.
Pandey and his team used a gene-editing tool called CRISPR-dCas9 in their experiments to manipulate the histone acetylation and methylation processes at the Arc gene in adult rat models. These processes make genes more or less accessible for activation.
First, the researchers studied adult rats with intermittent exposure to alcohol in their adolescence, which corresponds to about 10 to 18 years in human years. They noted that when dCas9 was used to promote acetylation, a process that detaches chromatin and allows transcription factors to bind to the DNA, Arc gene expression became normalized. In addition, the indicators of anxiety and alcohol consumption decreased.
Anxiety was measured by behavioral testing, such as by documenting the exploratory activity of rats placed in maze tests, and alcohol preference was measured by monitoring the amount of liquid consumed when the rats were presented with a choice of two bottles consisting of options such as tap water, sugar water and varying concentrations of alcohol (3%, 7% and 9%).
In a second model, the researchers studied adult rats without early exposure to alcohol. When inhibitory dCas9 was used to promote methylation, which tightens chromatin and prevents transcription factors from binding to DNA, Arc expression decreased and indicators of anxiety and alcohol consumption increased.
“These results demonstrate that epigenomic editing in the amygdala may improve adult psychopathology following alcohol exposure in adolescents,” the authors report.
“Adolescent big drinking is a serious public health problem, and this study not only helps us better understand what happens in developing brains when exposed to high concentrations of alcohol, but most importantly, gives us hope that we can will one day have effective treatments for the complex and multifaceted diseases of anxiety and alcohol use,” said Pandey, who is also a senior investigator at Jesse Brown VA Medical Center. “That this effect was seen bidirectionally confirms the significance of the Arc enhancer gene in the amygdala in epigenetic reprogramming of binge drinking in adolescents.”
Co-authors of the study, “Targeted epigenomic editing alleviates anxiety in adults and excessive drinking after alcohol exposure in adolescents,” are John Peyton Bohnsack, Huaibo Zhang, Gabriela Wandling, Donghong He, Evan Kyzar, and Amy Lasek, all of UIC.
Binge drinking in adolescence may increase the risk of anxiety later in life
John Peyton W. Bohnsack et al, Targeted epigenomic editing alleviates adult anxiety and excessive drinking after alcohol exposure in adolescents, scientific progress (2022). DOI: 10.1126/sciaadv.abn2748
Provided by the University of Illinois at Chicago
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