Microglia Show Distinct Behavior in Individuals at High Risk for Alcohol Use Disorder

Rutgers Health researchers have uncovered significant differences in how brain immune cells respond to alcohol exposure in individuals with high genetic risk for alcohol use disorder (AUD) compared to those with low risk. This research, published in Science Advances, provides new insights into the biological mechanisms underlying AUD susceptibility.

The study, led by Zhiping Pang, transformed blood cells from high-risk and low-risk individuals into microglia, a type of brain immune cell. When exposed to alcohol levels mimicking those in the blood after drinking, the microglia from high-risk individuals showed markedly increased activity compared to those from low-risk individuals.

Xindi Li, the study's lead author, noted that the highly active cells engaged in more "synaptic pruning"—removing connections between neurons. This increased pruning activity could have long-term implications. "After many years of drinking, people with these genetics may have a greater risk of dementia because the microglia pruned so many more connections," Li said. "Their overactivity could make neurons less functional."

While this study focused on a single type of brain cell in a simplified environment, the team is developing more sophisticated models for future research. “We're going from the cell cultures in a 2D situation to the brain organoids," Pang said. "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."

The findings suggest potential for personalized treatments for AUD based on genetic variations. However, the researchers emphasized that considerable work remains to translate these cellular findings into clinical applications.