MAR 06, 2023 6:21 PM PST

How Heavy Alcohol Use Causes Inflammation in the Brain

WRITTEN BY: Carmen Leitch

Alcohol use disorder (AUD) is a chronic disease with a cyclical nature; individuals compulsively consume alcohol, lose control over how much they drink, and are in a negative emotional state when they're not consuming alcohol. It may refer to binge drinking, alcohol dependence or abuse. Changes occur in the brains of people with AUD. There are reductions in the volume of the prefrontal cortex and deficits in prefrontal tasks like decision-making and emotional processing. Signaling alterations can occur that make problem drinking worse. Scientists have now learned more about a player in this cycle: the immune system. Reporting in Brain, Behavior and Immunity, scientists have determined that the brains of mice with alcohol dependence carry abnormally high levels of a signaling molecule called interleukin 1β (IL-1β). This molecule also behaves differently under these circumstances, and promotes inflammation in areas of the brain that are related to decision-making.

Researchers discovered higher than usual levels of the immune signaling molecule interleukin 1β (green) in neurons (outlined in red) from the brains of alcohol-dependent mice. / Credit: Scripps Research

“These inflammatory changes to the brain could explain some of the risky decision-making and impulsivity we see in people with alcohol use disorder,” said senior study author Marisa Roberto, PhD, a Professor and Chair at Scripps Research. “In addition, our findings are incredibly exciting because they suggest a potential way to treat alcohol use disorder with existing anti-inflammatory drugs targeting the IL-1β pathway.”

Previous work has indicated that the immune system is linked to AUD, and IL-1β seemed to be involved in this relationship. People are at higher risk for AUD when they carry mutations in the gene that encodes for IL-1β. Autopsies of people with AUD have also revealed unusually high IL-1β levels in the brain.

When a mouse model of alcohol dependence was compared to animals who did not drink or drank only moderate levels of alcohol, the investigators found that IL-1β levels were about twice as high in the medial prefrontal cortex (mPFC), which helps regulate emotions and behaviors.

Additional work showed that IL-1β had fundamentally changed in the mice modeling AUD. IL-1β usually activates an anti-inflammatory signaling pathway, and did so in mice that did not drink or drank moderately. Levels of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter that helps control neural activity in the brain were reduced by IL-1β.

But in the mice dependent on alcohol, IL-1β promoted inflammatory signaling and raised GABA levels, which probably causes some of the AUD-associated brain activity changes. The changes in IL-1β signaling persisted in the alcohol-dependent mice even when they withdrew from alcohol.

IL-1β blockers are already FDA-approved as a treatment for inflammatory disorders like rheumatoid arthritis. While more research is necessary to confirm these findings in people, IL-1β blockers may help people who are struggling with AUD.

Sources: Scripps Research Institute, Brain Behavior and Immunity

About the Author
Bachelor's (BA/BS/Other)
Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
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