Overthrowing cognition, Chinese scholars revealed the neurometabolic mechanism of alcohol for the first time in the world

In our country’s wine culture has a long history, almost every festive meal, family and friends gatherings have two drinks.

xianjiu

xianjiu

The liver is the main organ for alcohol detoxification.

Precise

Recently, the team of Professor Zhang Ye from the Department of Anesthesiology and Perioperative Medicine of the Second Affiliated Hospital of Anhui Medical University and Professor Zhang Li from the Institute of Alcohol Abuse and Alcoholism of the National Institutes of Health jointly published a study on Nature Metabolism, which revealed Alcohol causes brain function and behavioral disorders.

ALDH2 catalyzes the production of acetate from alcohol in the brain, which is the main cause of neurotransmitter changes and behavioral effects in the brain caused by alcohol.

Brain ethanol metabolism by astrocytic ALDH2 drives the behavioural effects of ethanol intoxication.

Brain ethanol metabolism by astrocytic ALDH2 drives the behavioural effects of ethanol intoxication.

The expression of ALDH2 in astrocytes in the cerebellum.

The expression of ALDH2 in astrocytes in the cerebellum.

In Aldh2Gfap−/− mice, acetate and GABA (an important inhibitory neurotransmitter) did not increase.

Schematic diagram of the metabolic pathway of ethanol to acetic acid in the liver and brain .

Schematic diagram of the metabolic pathway of ethanol to acetic acid in the liver and brain .

Acetic acid alone is sufficient to increase the level of GABA in mouse brain tissue and mediate alcohol-induced dyskinesia through the GABAergic mechanism, which proves that there is a connection between ALDH2 in astrocytes and GABA synthesis and its signaling pathways.

The acetic acid produced in the brain and the liver have different abilities to affect motor function.

The results of the entire study overturned previous cognition, indicating that acetic acid is an alcohol metabolite related to dyskinesia.

Acetic acid is an alcohol metabolite related to dyskinesia.

The ALDH2 enzyme has different roles in the liver and brain.

Astrocyte ALDH2 may be a useful target for the treatment of alcoholism.
It can be used to regulate the expression of astrocyte ALDH2 to help relieve alcohol, abstain from alcohol, and prevent and treat alcohol-induced brain injury and degeneration .
At the same time, it opens up a new direction for studying the related mechanisms of drunken behavior, and can also provide references for the pathogenesis and treatment of neurological diseases such as dementia (Alzheimer's syndrome).
Astrocyte ALDH2 may be a useful target for the treatment of alcoholism.
It can be used to regulate the expression of astrocyte ALDH2 to help relieve alcohol, abstain from alcohol, and prevent and treat alcohol-induced brain injury and degeneration .
At the same time, it opens up a new direction for studying the related mechanisms of drunken behavior, and can also provide references for the pathogenesis and treatment of neurological diseases such as dementia (Alzheimer's syndrome).
prevention

In fact, the research results are particularly important for Asians, especially East Asians.
In 2020, a joint research team from several Japanese institutions such as the University of Tokyo and the National Cancer Institute in Japan published a study in Science Advances, which pointed out that ALDH2 gene mutations are related to redness on the back of drinking, and people who blush after drinking are at risk of gastric cancer .
Bigger.

Stomach cancer

In this cross-ethnic study, researchers sequenced the genomes of 531 gastric cancer patients (319 Asian and 212 non-Asian) and divided them into 6 groups based on the mutation characteristics of the tissue samples, Signature 1, 3, 6, 15, 16, 17.
The analysis found that in the Signature 16 group, 70% of patients carried ALDH2 gene mutations, and more than 90% of the patients were Asians, and the average alcohol consumption of patients in this group was not high.
This also means that patients with ALDH2 gene mutations, even if they only drink a small amount of alcohol, will have a significantly increased risk of gastric cancer.

, In the Signature 16 group, 70% of patients carrying the ALDH2 gene mutation, wherein more than 90% of patients were Asian, and this group of patients is not high average drinker.
This also means that patients with ALDH2 gene mutations, even if they only drink a small amount of alcohol, will have a significantly increased risk of gastric cancer.
, In the Signature 16 group, 70% of patients carrying the ALDH2 gene mutation, wherein more than 90% of patients were Asian, and this group of patients is not high average drinker.
This also means that patients with ALDH2 gene mutations, even if they only drink a small amount of alcohol, will have a significantly increased risk of gastric cancer.
In the Signature 16 group, 70% of patients carry ALDH2 gene mutations, and more than 90% of the patients are Asians, and the average alcohol consumption of patients in this group is not high.
This also means that patients with ALDH2 gene mutations, even if they only drink a small amount of alcohol, will have a significantly increased risk of gastric cancer.

Signature1,3,6,15,16,17 gene mutation analysis.
Defined lifestyle and germline factors predispose Asian populations to gastric cancer.
DOI: 10.
1126/sciadv.
aav9778

Signature1,3,6,15,16,17 gene mutation analysis.
Defined lifestyle and germline factors predispose Asian populations to gastric cancer.
DOI: 10.
1126/sciadv.
aav9778

The distribution of ALDH2 gene in different populations around the world is significantly different.
According to researchers from the National Institute of Alcoholism and Alcoholism in the United States and the Kurihama Alcohol Research Center in Japan, about one-third of East Asians lack ALDH2, and about 40% of Asians have genetic defects in alcohol metabolism .
People who carry an ALDH2*2 gene, the ALDH enzyme activity is only 6% of the normal, while the two genes are all ALDH2*2, the ALDH enzyme activity is almost zero, which is the legendary "pour a cup.
"

About one-third of East Asians lack ALDH2, and about 40% of Asians have genetic defects in alcohol metabolism.
About one-third of East Asians lack ALDH2.
About 40% of Asians have alcohol metabolism.
genetic defect

The Alcohol Flushing Response: An Unrecognized Risk Factor for Esophageal Cancer from Alcohol Consumption.
doi: 10.
1371/journal.
pmed.
1000050

The Alcohol Flushing Response: An Unrecognized Risk Factor for Esophageal Cancer from Alcohol Consumption.
doi: 10.
1371/journal.
pmed.
1000050

The highest among them is the Han nationality in Guangdong, which is as high as 31%, and it is rare in European and American populations.

ALDH2 * Geographical distribution of 504Lys allele frequency.
The gray scale indicates the allele distribution frequency, and the hollow red triangle indicates the position of the overall sample.
The surrounding black lines indicate the frequency boundaries of the 0.
12 and 0.
24 distributions.
Refined Geographic Distribution of the Oriental ALDH2*504Lys(nee487Lys) Variant.
doi:10.
1111/j.
1469-1809.
2009.
00517.
x

ALDH2 * Geographical distribution of 504Lys allele frequency.
The gray scale indicates the allele distribution frequency, and the hollow red triangle indicates the position of the overall sample.
The surrounding black lines indicate the frequency boundaries of the 0.
12 and 0.
24 distributions.
Refined Geographic Distribution of the Oriental ALDH2*504Lys(nee487Lys) Variant.
doi:10.
1111/j.
1469-1809.
2009.
00517.
x

In summary, for a long time, a large amount of data has proved that drinking is harmful to health.
With the development of medicine, the core metabolic mechanism of drunkenness-related behaviors such as behavioral disorders after drinking has gradually become clear.
For the general public, abstaining from alcohol and limiting alcohol is the most important.

For a long time, a large amount of data has proved that drinking is harmful to health.
With the development of medicine, the core metabolic mechanism of drunkenness-related behaviors such as behavioral disorders after drinking has gradually become clear.
For the general public, abstaining from alcohol and limiting alcohol is the most important.
For a long time, a large amount of data has proved that drinking is harmful to health.
With the development of medicine, the core metabolic mechanism of drunkenness-related behaviors such as behavioral disorders after drinking has gradually become clear.
For the general public, abstaining from alcohol and limiting alcohol is the most important.
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