pour one out

Scientists find a troubling link between binge drinking and brain dysfunction

Excessive alcohol can disrupt brain signaling, fueling anxiety.

Alcohol often feels good in the moment, but drinking too much of it and too often can strain mental and physical health.

Heavy drinking can take a toll on the body, heightening the risk of health issues like high blood pressure and cancer. Excessive imbibing can also dangerously affect the brain, capable of driving cognitive-behavioral issues like anxiety.

In a recent study in mice, researchers discovered the underlying mechanism driving post-binging anxiety specifically.

They found that 10 days of binge drinking — the equivalent of five drinks daily for the average adult — spurred immune cells in mice brains to destroy connections between neurons, leading to anxiety and other cognitive issues.

Study co-author João Relvas, a researcher at the University of Porto, tells Inverse although the research was conducted in mice, scientists "don’t have any reason to believe that the same mechanisms will not be operating in the human brain."

"Even for a short period of time, excessive drinking is likely to affect the brain, increasing the level of anxiety, a relevant feature in alcohol abuse and addiction," Relvas says. His team's findings were published Wednesday in the journal Science Signaling.

The exact drinking patterns that spark synaptic dysfunction could be revealed in further experiments, conducted in humans. For now, Relvas cautions that people should pay attention to their intake and follow public health guidelines on drinking in moderation.

"The dangers of alcohol drinking, especially amongst the younger population, have been widely underestimated and excessive alcohol drinking is socially relatively well tolerated," Relvas says.

"Increasing public awareness and education of the young can, together with other measures, change the way society looks at alcohol intake."

Alcohol and microglia — Previous studies show binge drinking can have lasting, negative impacts on brain functioning. This team honed in on synaptic functioning, or how effectively nerve cells signal to each other, as a driving factor behind this negative connection.

Past research also suggests that microglia (immune cells in the brain) tend to become hyperactive in the brains of alcohol abusers. But until now, how these microglia influence synaptic functioning and potential alcohol-induced brain damage has been unclear.

"The dangers of alcohol drinking, especially amongst the younger population, have been widely underestimated... "

To determine how drinking influences microglia, researchers administered alcohol or water to male mice via tubes for 10 consecutive days. They gave half the mice 1.5 grams per kilogram of ethyl alcohol daily — a dose equal to five drinks for an adult person who weighs 165 pounds. This number simulates binge drinking's effect on the human mind and body.

After ten days of drinking alcohol or water, scientists analyzed the mice's brain tissue. They found that alcohol triggered microglia to engulf and destroy connective synapses between neurons in the prefrontal cortex, the area of the brain that controls complex cognition and decision making.

This synaptic dysfunction resulted in increased anxiety-like behavior.

Peering inside the brain — Further experiments showed that alcohol put microglia into this destructive mode by boosting the production of an inflammatory molecule called TNF. The team then blocked TNF production with an approved drug called pomalidomide. In turn, this drug prevented anxiety and the destruction of synapses.

This synaptic dysregulation is "ultimately driven by increased secretion of TNF by microglia, as we show that reducing its production either pharmacologically or genetically can prevent synapse loss and anxiety," Relvas explains.

"This study suggests that regulating the levels of TNF might eventually be useful when treating alcohol addiction."

Microglia that were exposed to alcohol engulfed more synaptosomes in the prefrontal cortex.

R. Socodato, et. al, "Science Signaling"

However, how this finding will actually influence future treatments is currently uncertain. For now, the team does not advocate using TNF inhibitors as a way to help people who binge drink avoid elevated anxiety.

That's because binge drinking has a vast cascade of negative health effects on the heart, liver, pancreas, and immune system. A TNF inhibitor would only tackle one dimension of the problem. Eventually, a holistic treatment that incorporates this new discovery is the goal.

What to do about binge drinking now — Ultimately, rather than waiting for a novel therapeutic, people should instead focus on drinking in moderation, or not drinking at all.

Relvas recommends following your country's public health guidelines for alcohol, as the substance is one of the world's leading causes of premature death and disability. Globally, it causes nearly three million deaths every year.

According to the "Dietary Guidelines for Americans 2015-2020,” a collection of recommendations and data pulled together by the U.S. Department of Health and Human Services and U.S. Department of Agriculture, moderate drinking is up to one drink per day for women and up to two drinks per day for men.

"Alcohol abuse is a leading cause of disease with a massive impact on human life and should be treated as so," Relvas says.

Abstract: Alcohol abuse adversely affects the lives of millions of people worldwide. Deficits in synaptic transmission and in microglial function are commonly found in human alcohol abusers and in animal models of alcohol intoxication. Here, we found that a protocol simulating chronic binge drinking in male mice resulted in aberrant synaptic pruning and substantial loss of excitatory synapses in the prefrontal cortex, which resulted in increased anxiety-like behavior. Mechanistically, alcohol intake increased the engulfment capacity of microglia in a manner dependent on the kinase Src, the subsequent activation of the transcription factor NF-kB, and the consequent production of the proinflammatory cytokine TNF. Pharmacological blockade of Src activation or of TNF production in microglia, genetic ablation of Tnf, or conditional ablation of microglia attenuated aberrant synaptic pruning, thereby pre- venting the neuronal and behavioral effects of the alcohol. Our data suggest that aberrant pruning of excitatory synapses by microglia may disrupt synaptic transmission in response to alcohol abuse.
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