A 'factory reset' for the brain may cure anxiety, drinking behavior,
study suggests
Gene editing reverses brain genetic reprogramming caused by adolescent
binge drinking
Date:
May 4, 2022
Source:
University of Illinois Chicago
Summary:
Gene editing may be a potential treatment for anxiety and alcohol
use disorder in adults who were exposed to binge drinking in their
adolescence, according to the results of an animal study. The
researchers used a gene-editing tool called CRISPR-dCas9 in their
experiments to manipulate the histone acetylation and methylation
processes at the Arc gene in models of adult rats.
FULL STORY ==========================================================================
Gene editing may be a potential treatment for anxiety and alcohol
use disorder in adults who were exposed to binge drinking in their
adolescence, according to the results of an animal study published in
the journal Science Advances.
==========================================================================
The study is issued by researchers from the University of Illinois Chicago
who have been 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 at the enhancer region of the Arc gene -- for
activity- regulated cytoskeleton-associated protein immediate-early gene
-- and decreases Arc expression in the amygdala of both rodents and
humans. This epigenetic reprogramming of the Arc gene in the brain's
emotion and memory center contributes to a predisposition to anxiety
and alcohol use disorder in adulthood.
In the new study, the researchers show that this epigenetic reprogramming, which persists throughout life, actually can be reversed with gene
editing.
"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," said study 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 models of adult rats. These processes make
genes more or less accessible for activation.
First, the researchers studied adult rats with intermittent alcohol
exposure in their adolescence, corresponding to about age 10 to 18
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 the 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 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
alcohol exposure. 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 can ameliorate adult psychopathology after adolescent alcohol exposure,"
the authors report.
"Adolescent binge drinking is a serious public health issue, and this
study not only helps us better understand what happens in developing
brains when they are exposed to high concentrations of alcohol but
more importantly gives us hope that one day we will have effective
treatments for the complex and multifaceted diseases of anxiety and
alcohol use disorder," said Pandey, who is also a senior research career scientist at Jesse Brown VA Medical Center. "That this effect was seen bidirectionally validates the significance of the Arc enhancer gene in
the amygdala in epigenetic reprogramming from adolescent binge drinking."
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: Materials provided by University_of_Illinois_Chicago. Note: Content may be edited for style and length.
========================================================================== Journal Reference:
1. John Peyton W. Bohnsack, Huaibo Zhang, Gabriela M. Wandling,
Donghong He,
Evan J. Kyzar, Amy W. Lasek, Subhash C. Pandey. Targeted epigenomic
editing ameliorates adult anxiety and excessive drinking after
adolescent alcohol exposure. Science Advances, 2022; 8 (18) DOI:
10.1126/ sciadv.abn2748 ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2022/05/220504153619.htm
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