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Scientists have explained why alcohol disrupts coordination
Maria Krivochenko, Naked Science
Acetate is a metabolite of ethanol, which is produced by the enzyme aldehyde dehydrogenase (ALDH2). It interacts with gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter of the central nervous system. He is also responsible for how a drunk person behaves. For example, people who blush from alcohol have a deficiency of ALDH2. So they can't produce acetate quickly.
Previously, it was believed that ethanol metabolism occurs in the liver, and decay products already enter the brain. However, a group of American neuroscientists from the Institute of Alcoholism of the National Institutes of Health of the USA found out that acetate oxidation can also occur in the brain. It turned out that it is expressed in the astrocytes of the cerebellum and causes a loss of coordination. Details of the discovery are published in the journal Nature Metabolism (Jin et al., Brain ethanol metabolism by astrocytic ALDH2 drives the behavioral effects of ethanol intoxication).
The scheme of ethanol metabolism in the liver (bottom) and in the brain (right) / © Jin et al.
The researchers studied the expression of ALDH2 mRNA in various brain regions on 11 slices of mouse brain tissue and three slices of human brain tissue. It turned out that most of the expression is expressed in the cerebellum, and least of all in the prefrontal cortex.
The team also conducted an experiment on mice. To do this, scientists bred rodents whose brains did not have the enzyme ALDH2. Then they and ordinary animals were given a small amount of ethanol (one gram per kilogram of weight). During the analysis, it turned out that alcohol stimulates the appearance of acetate in the cerebellum. However, the bred mice turned out to be more resistant to alcohol, since the enzyme almost did not convert alcohol into acetate, which accumulated in the brain. Rodents without astrocytic ALDH2 also had lower levels of GABA in the brain after drinking alcohol. Hence, better coordination.
This dependence was not observed in mice with liver enzyme deficiency. This allowed the authors of the study to assume that the source of acetate in the cerebellum is alcohol, not aldehyde. But this has yet to be proven.
Finally, scientists came to the conclusion that the enzyme ALDH2, located in the liver and brain, affects the body in different ways. They intend to continue research on this enzyme in humans. Experts also called astrocytic ALDH2 an important target for the treatment of alcohol addiction and neurological diseases.
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