According to a new study published by researchers from Rutgers University, brain immune cells called microglia from individuals with a high genetic risk for alcohol use disorder (AUD) behave differently compared to cells from individuals with a lower risk for developing AUD when exposed to alcohol.

The findings of the study, published in the journal Science Advances, could help explain the individual differences in susceptibility to developing AUD and help to develop personalized treatment approaches.

“This is the first study to show how the genetic variations that increase the risk of AUD affect the behaviour of some brain cells,” said Dr. Zhiping Pang, a professor of neuroscience and cell biology at Robert Wood Johnson Medical School and a resident scientist at the Child Health Institute of New Jersey and a core member at the Rutgers Brain Health Institute, in a press release. “We started with a simple model, but as the models get more complex, we’ll learn more about what’s happening in the brain. Hopefully, our discoveries will suggest treatment approaches because we don’t currently have great treatments for AUD.”

As part of the research, scientists collected blood samples from two groups of study participants, including individuals with a high genetic risk for AUD and diagnosed alcohol problems, as well as from individuals with low genetic risk and no diagnosed alcohol use problems. The cells were then transformed into stem cells and subsequently differentiated into microglia.  

Then, the cells were exposed to alcohol levels comparable to those seen in the blood following alcohol use. It was found that microglia with high genetic risk scores were significantly more active than microglia with low genetic risk scores after alcohol exposure. Moreover, the study results revealed that the active microglia removed significantly more connections between brain cells, a phenomenon called “synaptic pruning.”

“After many years of drinking, people with these genetics may have a greater risk of dementia because the microglia pruned so many more connections,” said Dr. Xindi Li, lead author of the study, a postdoctoral fellow at the Child Health Institute of New Jersey. “Their overactivity could make neurons less functional.”

Currently, the study authors are developing more sophisticated models for their research. “We’re going from the cell cultures in a 2D situation to the brain organoids,” said Dr. Pang. “So we can study something more like a mini brain-structure, to understand how the cells interact with alcohol, and then to see how the genetic risk factors play a role in that response.”