A recent study sheds light on why certain individuals are more prone to alcohol-related issues.
Researchers at Rutgers Health have found that the brain immune cells in individuals with a high genetic predisposition for alcohol use disorder (AUD) react differently to alcohol compared to those with a low risk.
The findings published in Science Advances may help clarify the reasons behind varying susceptibility to drinking problems and could pave the way for personalized treatment options.
“This study is the first to illustrate how genetic variations that heighten the risk of AUD influence the behavior of certain brain cells,” stated 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, as well as a core member of the Rutgers Brain Health Institute.
“We began with a straightforward model, but as our research develops into more complex models, we’ll gain deeper insights into brain activity,” Pang, the senior author of the study, elaborated. “We hope our findings will lead to new treatment strategies since effective treatments for AUD are currently lacking.”
According to the 2023 National Survey on Drug Use and Health, about 28.9 million Americans aged 12 and older are affected by alcohol use disorder. While it has been established that AUD often runs in families, with genetic factors contributing to 40% to 60% of the risk, the biological mechanisms involved have remained largely unknown.
The research team collected blood samples from two groups: individuals with a high genetic risk for AUD who had been diagnosed with alcohol issues and those with a low genetic risk who did not have drinking problems. They converted these blood cells into stem cells, which then developed into a specific kind of brain immune cell known as microglia.
These cells from both groups were then exposed to alcohol levels that imitate those found in the bloodstream after consuming alcohol.
“The microglia from individuals with high genetic risk showed significantly higher activity levels compared to those with lower genetic risk after alcohol exposure,” explained Xindi Li, the lead author of the study and a postdoctoral fellow at the Child Health Institute of New Jersey.
These overly active cells participated more intensively in “synaptic pruning,” which involves eliminating connections between neurons in the brain. This increased pruning activity could have important consequences, according to the researchers.
“Prolonged alcohol use might elevate the risk of dementia in genetically predisposed individuals, as their microglia eliminate many more connections,” Li noted. “This overactivity could hinder neuronal functionality.”
The study harnessed the diverse expertise across Rutgers University, involving scientists from various labs and departments, including Ronald Hart and Jay Tischfield. This collaborative effort combines knowledge from genetics, neuroscience, and addiction research to address the intricate issue of how genetic risk factors impact alcohol use disorder at the cellular level. This research is part of the long-term Rutgers initiative within the larger NIH-funded Collaborative Study on the Genetics of Alcoholism (COGA).
While prior studies have pinpointed genetic variants linked to increased risk, it has been difficult to understand how these differences affect brain cell operations.
Although this research focused on a single type of brain cell in a controlled environment, the team is poised to develop more advanced models for further studies.
“We are advancing from basic cell cultures in two dimensions to brain organoids,” Pang mentioned. “This transition allows us to examine something resembling a mini brain structure to better understand how these cells interact with alcohol and how genetic risk factors influence that interaction.”
This research could ultimately lead to improved treatments for alcohol use disorder. The findings suggest that if various genetic factors result in differing cellular behaviors in the brain, individuals with distinct genetic profiles may benefit from tailored treatments, such as targeting microglia in high-risk individuals.
However, the researchers emphasized that significant efforts are still needed to translate these cellular insights into practical clinical applications.
