Long-term brain changes from just one drink!

Alcohol is the most regularly used addictive substance in the world. Only 5% of adults worldwide, according to inadequate statistics, do not consume alcohol at any point in their lives, and in addition to those who do, all other drinkers are thought to be at risk for developing alcohol addiction.

It is well known that as the amount and frequency of alcohol consumption increases, the risk of alcohol addiction and health damage increases as well. But can't a shallow taste do the trick? Can just one drink lead to addiction?

The answer is yes.

Single-dose ethanol intoxication causes acute and lasting neuronal changes in the brain, according to a study published in PNAS by German researchers, showing that even a single drink may permanently alter the morphology of neurons in the brain, particularly affecting the structure of hippocampal synapses and mitochondrial dynamics, thereby inducing the onset of alcohol addiction!

A single administration of only 50 mM of ethanol (the amount that causes acute alcohol intoxication) induced changes in the abundance levels of hippocampal synaptic proteins in the brain, which were more pronounced in young mice.

In the mouse hippocampus, 72 proteins, including malate dehydrogenase, monoamine oxidase A, GAP-43, and tyrosine protein kinase Fyn, showed substantial changes in response to ethanol stimulation. Additionally, ethanol boosted GABA signaling in the brain and decreased the synaptic abundance of the gamma-aminobutyric acid (GABA) reuptake transporter protein GAT4 and GABA transaminase. Notably, ankyrin-G and MAP6, two essential proteins for maintaining spinal integrity, were similarly impacted by acute ethanol exposure.

Overall, a single episode of acute alcohol intoxication altered multiple proteins in the mouse brain, affecting synaptic transmission and plasticity, mitochondrial function, apoptosis, and neurodegenerative disease. More seriously, alcohol damage is synaptically persistent, meaning that it persists even when mice have high levels of ethanol metabolism.

The researchers also observed a significant increase in mitochondrial mobility in the thalamus of mice after alcohol consumption: within 1h of acute alcohol intoxication, mitochondrial mobility in the brain increased significantly and peaked at 3h; and this effect of increased mitochondrial mobility was maintained for about 4h and did not return to baseline levels until a day later.

This higher mitochondrial mobility interferes with the normal movement of mitochondria and hinders the optimal energy transfer. This was manifested by a significant decrease in precise behavior, false alarm rate, efficiency, and performance, i.e., the mice walked crookedly, became slow to respond to unexpected events, and did things much less efficiently and with less completion when drunk, and this lasted for at least 48h.

The effect of ethanol on mitochondrial motility further alters the plasticity of neurons in the brain. The morphological remodeling of these neurons, which is the basis for learning and memory, is a crucial part of the process of alcohol addiction. This explains why just one "drunkenness" can lead to alcoholism and even addiction.

Professor Henrike Scholz, who led the study, said that the cellular processes that lead to this complex reward behavior show a high degree of similarity even across species, so the mechanisms of "alcoholism and addiction" can be extrapolated to humans. Thus, in individuals, "early first" intoxication is a key risk factor for alcoholism and addiction later in life.

In summary, animal studies have demonstrated that a single episode of acute ethanol intoxication leads to short- and long-term changes in synaptic protein and mitochondrial dynamics, further inducing neuronal changes associated with alcohol addiction, and that these effects are more pronounced early in life.