MSGID: 1:317/3 627352fd   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    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   
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   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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