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Underage drinking has lasting effects on the brain and epigenetics

underage drinking

The rise of underage drinking has almost left a sense that it is acceptable or even free of long-term consequences. Unfortunately because the brain continues forming long into the early twenties, environmental factors can have a large impact on the development. In fact, research shows that binge-drinking during adolescence may perturb brain development at a critical time and leave lasting effects on genes and behavior that persist into adulthood.

“This may be the mechanism through which adolescent binge-drinking increases the risk for psychiatric disorders, including alcoholism, in adulthood,” says lead author Subhash Pandey, professor of psychiatry and director of neuroscience alcoholism research at UIC.

Researchers used experimental rats to investigate the effects of intermittent alcohol exposure during the adolescent stage of development.

On-and-off exposure to alcohol during adolescence altered the activity of genes needed for normal brain maturation. The gene alterations increased anxiety-like behaviors and preference for alcohol in adulthood.

The behavioral effects were due to “epigenetic” changes — “which previous research has shown can be influenced through environmental substances, including alcohol.” Epigenetic changes can be long-lasting or even permanent in an individual. Previous studies have shown that some epigenetic changes can be heritable.

Epigenetic changes are chemical modifications of the DNA or of the proteins around which DNA is wound, like thread on a spool. Modification of these proteins, called histones, can change how loosely or tightly the DNA is wound. Genes that lie within DNA that is tightly wrapped around the histones are less active than they are if the DNA is loosely wrapped. The looser the DNA is coiled, the more accessible are the genes to the cellular machinery that “expresses” them.

Epigenetic changes regulate many processes, including brain development and maturation during adolescence. Changes to the histones expose the genes needed to form new synaptic connections, or to prune unneeded neurons.

To model adolescent binge-drinking in humans, the researchers gave 28-day-old rats alcohol for two days in a row, followed by two days off, and repeated this pattern for 13 days. Some rats were followed into adulthood and observed for abnormal behaviors. They were offered both alcohol and water, and their alcohol-drinking behavior was monitored.

Rats exposed to alcohol during adolescence exhibited changes in behavior that lasted into adulthood, long after exposure to alcohol ended. They showed increased anxiety-like behaviors and drank more alcohol in adulthood.

When the researchers analyzed tissue from a part of the brain called the amygdala, they found in the exposed rats that the DNA and histones appeared to be tightly wrapped. They also found increased levels of a protein called HDAC2, which modifies histones in a way that causes DNA to be wound tighter around them.

These epigenetic changes in turn were linked to lowered expression of a gene that nerve cells need in order to form new synaptic connections. Pandey believes the lowered activity of this gene may be due to the tighter winding of its DNA. The diminished expression of the gene persisted in adulthood, even if alcohol exposure was stopped weeks before. The researchers observed diminished nerve connectivity in the amygdalae of these affected adult rats.

“Our study provides a mechanism for how binge-drinking during adolescence may lead to lasting [epigenetic] changes … that result in increased anxiety and alcoholism in adults,” Pandey said. “

“[Intermittent alcohol exposure] degrades the ability of the brain to form the connections it needs to during adolescence.”

“The brain doesn’t develop as it should, and there are lasting behavioral changes associated with this.”

However, a pharmacological experiment hinted at the possibility of a treatment. When adult rats that had been exposed to alcohol during adolescence were given a cancer drug known to block the activity of HDAC2, the drug restored expression of the gene needed for synapse formation. The DNA was observed to be less tightly coiled, as expected.

Most importantly, the rats exhibited less anxiety and reduced alcohol intake.

“We aren’t sure if the drug needs to be given long term during adulthood in order to completely reverse the harmful effects of adolescent alcohol exposure,” Pandey said.

Further experiments with this and other epigenetic drugs are planned.

Sources:
Pandey SC, Sakharkar AJ, Tang L, & Zhang H (2015). Potential role of adolescent alcohol exposure-induced amygdaloid histone modifications in anxiety and alcohol intake during adulthood. Neurobiology of disease PMID: 25814047

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3 responses

  1. bhogan

    I have seen the effects of alcohol on people long and short term while working as a paramedic. We would run people that were alcoholics or were recovering alcoholics. Even when they were not drinking for drunk they do not act right. They seem slower than the normal person. They have a hard time answering questions and doing simple movements.

    April 5, 2015 at 6:52 pm

    • That’s rough, I hate seeing people suffer like that. Thanks for sharing your story and for being a paramedic.

      April 6, 2015 at 12:35 pm

  2. kelly

    This article is discussing the effects binge drinking as an adolescence can cause to the brain. It also states threat it can lead to alcoholism and psychiatric disorders later in life. The brain is still trying to develop as an adolescent and when alcohol is consumed it can lead to long lasting behavioral issues as well. I have always heard that alcohol isn’t good for these exact reason, but reading this article and see the changes in just rats, it amazes me. Not only does underage drinking interfere with the development of the brain, it can also cause epigenetics. This is involved with DNA and if it gets worse it can eventually cause cancer. I think this article should be shared with teenagers all over, however according to Erik Erickson, at this stage adolescents think they things like this will never happen to them. during this stage in life the are risk takers and just want to fit in, even if it means binge drinking which can cause death alone. on top of that that are facing identity versus role confusion. Drinking may be a way one fits in and might assume that that is their role. I chose to write about this because I myself was a teenager once and to look back and realize the harmful events that could take place from drinking with a friend really hit home.

    September 1, 2015 at 7:29 pm

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