Think binge-drinking is no big deal? Research has shown it can cause lasting cognitive decline in teens and young adults—but a new study by a Duke researcher found that a common Alzheimer’s drug could be used to reverse these dangerous brain changes.
Drinking during adolescence can cause both structural and genetic damage in the neurons of the brain, specifically in the hippocampus which is linked to learning and memory. However, Scott Swartzwelder, professor in psychiatry and behavioral sciences, found that giving rats the drug donepezil can reverse the damage. Donepezil is frequently used to improve cognitive function in patients with Alzheimer's disease.
“What we’re interested in is the long-term effects of alcohol exposure in adolescence,” Swartzwelder said. “The core question is, when young people drink alcohol on a regular basis, are there long-lasting effects that persist into adulthood?”
The study was published in the journal “Alcoholism: Clinical and Experimental Research” and was supported by the National Institute on Alcohol Abuse and Alcoholism.
The researchers found that when adult rats had been exposed to alcohol as adolescents, they had far fewer dendritic spines as adults. These spines stem from neurons to receive information in the brain.
“If you don't have enough [dendritic spines], that really compromises the ability of that cell to process information,” Swartzwelder said. “If you knock down the ability of one cell, it has a downstream effect on other cells.”
While rats who hadn’t been exposed to alcohol had a dense mass of dendritic spines, those in rats previously exposed to alcohol were sparse and stubby.
However, when these rats were given the drug donepezil, these changes appeared to reverse, Swartzwelder explained. He noted that this finding could potentially be translated to the clinic because the drug is regarded as safe and is commonly used.
“What was really exciting was that post treatment of the animals that were exposed to alcohol, donepezil completely reversed changes in the microstructure of the brain cells,” said Patrick Mulholland, an author of the study and professor at the Medical University of South Carolina in the department of neurosciences and the Charleston Alcohol Research Center.
The team also found that changes in the dendritic spines were connected to the Fmr1 gene, which is linked to developmental delays and learning disabilities.
“Interestingly, what we found is that there were changes in expression of the gene due to alcohol exposure,” Swartzwelder said. “Those changes also reversed with donepezil.”
He explained that this finding gives scientists a specific gene to study moving forward and to see if it is a mechanism driving changes in dendritic spines.
“Any time you can identify a specific mechanism that is associated with this effect, you have a very powerful potential target that you can pursue to develop treatments,” he said.
Mulholland noted that the research has the potential to impact treatment for humans.
“It’s a long shot to go from a rat to a human and is difficult to do, but the study that was published is suggestive that donepezil may be a viable treatment option,” he said.
In the future, Swartzwelder said he hopes to continue studying the Fmr1 gene connection, as well as other genes that might be related to dendritic spines and whether other drugs could be used to reverse the changes caused by alcohol.
Collectively, their study highlights how drinking during adolescence might impact cognitive ability later in life.
“From a public education standpoint, it’s really important that people understand that when young adults drink and they drink in heavy binge patterns, there are consequences downstream,” Swartzwelder said.
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