Tuesday, March 21, 2023

A ‘factory reset’ for the brain may fix anxiety, drinking behavior, study shows: Gene editing reverses brain genetic reprogramming caused by adolescent binge drinking

Gene editing may be a potential treatment for anxiety and alcohol use disorder in adults who were exposed to binge drinking in their teens, according to the results of an animal study published in the journal Science. science advance.

The study continues by researchers at the University of Illinois at Chicago who are studying the effects of early life binge drinking on health later in life.

In prior research, the UIC team found that binge drinking in adolescence alters brain chemistry in the enhancer region of the Arc gene — the activity-regulated cytoskeleton-related protein for immediate-early genes — and Arc expression in the amygdala of both rodents. reduces. and man. This epigenetic reprogramming of the Arc gene in the brain’s emotion and memory center contributes to a predisposition for anxiety and alcohol use disorder in adulthood.

In the new study, researchers show that this epigenetic reprogramming, which persists throughout life, may actually be reversed by gene editing.

“Early binge drinking can have a long-lasting and significant effect on the brain, and the results of this study provide evidence that gene editing is a potential antidote to these effects, if you wish, as a brainwashing agent.” kind of factory reset,” he said. Study senior authors Subhash Pandey, Joseph A. Flaherty studied 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 histone acetylation and methylation processes in the Arc gene in adult mice models. These processes make genes more or less accessible for activation.

First, the researchers studied adult rats with intermittent alcohol exposure in their teens, which corresponds to approximately 10 to 18 years of age in human years. They observed that when dCas9 was used to promote acetylation, a process that loosens chromatin and allows transcription factors to bind to DNA, Arc gene expression normalized. And, indicators 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. Presented were alternatives 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 strengthens chromatin and prevents transcription factors from binding to DNA, Arc expression decreased and indicators of anxiety and alcohol consumption increased.

“These results suggest that epigenomic editing in the amygdala may improve adult psychopathology after exposure to adolescent alcohol,” report the authors.

“Adolescent drinking is a serious public health problem, and this study not only helps us understand what happens in the developing brain when they are exposed to high concentrations of alcohol, but more importantly, how We hope that one day we will have effective treatments. “The complex and multifaceted disease of anxiety and alcohol use disorder,” said Pandey, a senior research career scientist at the Jesse Brown VA Medical Center. Binge drinking validates the importance of Arc enhancer genes in the amygdala in epigenetic reprogramming.”

The research was supported by the National Institute on Alcohol Abuse and Alcoholism (U01AA019971, U24AA024605, P50AA022538, and F32AA027410) and the Department of Veterans Affairs.

Story Source:

material provided by University of Illinois Chicago, Note: Content can be edited for style and length.


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