Ten percent of adolescents and young adults aged 12 to 20, whose brains are still developing, report drinking alcohol, with 90% of their consumption being binge drinking, according to the National Institute on Alcohol Abuse and Alcoholism (NIAAA). An interdisciplinary team of researchers at Penn State will use a new five-year, $2,900,000 grant to investigate the long-term effects of excess alcohol drinking during adolescence.
Awarded by the National Institutes of Health's NIAAA, the grant will fund work in mice to better understand the chemical and biological impacts voluntary binge drinking has on the brain.
"We are really interested in healthy development of the adolescent brain," said principal investigator Nikki Crowley, director of the Penn State Neuroscience Institute at University Park, Huck Early Career Chair in Neurobiology and Neural Engineering and assistant professor of biology and of biomedical engineering. "We are also interested in understanding the things that disrupt the natural development and growth of the adolescent brain. This project is specifically looking at how, in a mouse model, adolescent exposure to binge drinking could change the way in which the brain develops."
Crowley is collaborating with Nanyin Zhang, the Dorothy Foehr Huck and J. Loyd Huck Chair in Brain Imaging and professor of biomedical engineering; Nikki Beloate, assistant research professor; and Justin Silverman, Penn State Institute for Computational and Data Sciences co-hire, assistant professor of information sciences and technology, of statistics and of medicine. The project will also provide research opportunities for undergraduate and graduate students.
The research team will use multiple approaches - including imaging - to precisely measure and analyze activity and changes in the electrical and chemical signaling between neurons in the brain, as well as to examine impacts across the entire brain.
"This approach allows us to see in real time and with extreme biological depth, how a perturbation like alcohol consumption can change the wiring and firing of the brain," Crowley said.
While the research will be conducted in a mouse model, Crowley said the findings may have implications for humans. The model will look at how binge drinking during adolescence affects circuit-level development and brain-network development and how they are related to altered behaviors in animals, which could correlate to changes in behavior in humans.
The researchers are focused on specific neuron types, such as inhibitory, GABAergic cells called somatostatin neurons, which are involved in decision-making and executive function. These neurons undergo significant maturation and growth during the adolescent period and have been found to contribute to behaviors such as binge drinking, Zhang said. He explained that the team plans to explore how the neurocircuitry and pathways of various neurons, including somatostatin, are affected by post-alcohol exposure. The team also seeks to understand the long-term effects of alcohol exposure going into adulthood.
This builds upon previous work conducted by Crowley on adolescent binge drinking on adult brains in mice.
"Mouse models allow us to look at the same alcohol exposure patterns on the brain on a faster time scale, allowing and allow us to have a mechanistic, chemical depth of measurement that we can't do in humans," Crowley said. "Mice will have access to alcohol for small periods of time for a couple of days, and then will have periods of abstinence, just like a human would experience. It is also voluntary; the mice are not forced to have alcohol. This model allows us to solve questions that are directly related to human health."
The researchers will also examine how exposure to alcohol could potentially affect male and female mice differently.
"We want to look and identify if there is a sex-specific response to the exposure or if male and female animals react differently to the exposure," Zhang said.
According to Crowley, the researchers' goal is to not only shed light on the effects of binge drinking, but also to potentially identify potential targets for therapies in the future for individuals going through alcohol use disorder.
"By understanding the specific cellular changes adolescent brains experience after binge drinking, we have a starting place to begin thinking about how to mitigate long-term effects - or preemptively prevent them from occurring in the first place," Crowley said.
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