Metabolism: Alcohol is directly metabolized in the brain in mice
Nature Metabolism
March 23, 2021
The behavioural effects of alcohol intoxication may be caused by alcohol breakdown products (metabolites) produced in the brain, and not in the liver, in mice, according to a study published in Nature Metabolism. These findings provide new insights into how alcohol may affect the brain and open the possibility of better regulation of the effects of alcohol on behaviour.
The behavioural effects of alcohol, such as motor impairment, in people and mice are thought to be caused by metabolites produced during alcohol breakdown. One such metabolite, acetate, is produced by the enzyme ALDH2, which is abundant in the liver. Acetate produced in the liver travels via the bloodstream to the brain, where it can impair motor function through signalling via the inhibitory neurotransmitter GABA.
Li Zhang and colleagues observed that in three human brain samples and 11 mice, ALDH2 was expressed in cells known as astrocytes in the cerebellum, a brain region that controls balance and motor coordination. When ALDH2 was removed from the cerebellar astrocytes, the mice were resistant to the motor impairment induced by alcohol consumption. Normally, alcohol consumption elevates the levels of acetate and GABA in the brain; however, this elevation was prevented when ALDH2 was deleted from astrocytes. In contrast, removing ALDH2 in the liver did not affect the levels of acetate or GABA in the brain. These findings suggest that acetate produced in the brain and in the liver differ in their ability to affect motor function.
The authors conclude that alcohol metabolism may therefore be regulated directly in the brain, thus suggesting the possibility of new targets for altering alcohol’s effects and potentially treating alcohol use disorder. Further research is necessary to determine whether these mechanisms observed in mice also exist in people.
doi:10.1038/s42255-021-00357-z
Research highlights
-
Mar 29
Materials: Yolk proteins make an eggcellent addition to Old Masters’ oil paintingsNature Communications
-
Mar 28
Geoscience: Water on the Moon stored in beads of impact glassNature Geoscience
-
Mar 28
Health: Positive effects of regular physical exercise for cognition might be negligibleNature Human Behaviour
-
Mar 28
Environment: Microplastic consumption may alter seabird gut microbiomesNature Ecology & Evolution
-
Mar 24
Zoology: Numerical abilities may be hardwired in newly-hatched zebrafishCommunications Biology
-
Mar 23
Ecology: Australian reef species decline following decade of warmingNature