Geneticists' research will help treat alcoholism
"When sober, he has a "brain storm" going on"
Scientists caused alcoholism by mutation of one geneNadezhda Markina, <url>
About what genes are associated with alcoholism in humans, "The newspaper.Ru" said Svetlana Borinskaya, a leading researcher at the Institute of General Genetics of the Russian Academy of Sciences.
Addiction to alcohol largely depends on our genes, this not only follows from life experience, but is also convincingly proven by science. But there are many of these genes, and what contribution each of them makes, and most importantly, how exactly it acts, scientists have yet to figure out. But British researchers figured out one such gene by publishing an article in the latest issue of the prestigious journal Nature Communications: Anstee et al., Mutations in the Gabrb1 gene promote alcohol consumption through increased tonic inhibition (we recommend reading a popular summary in the Newcastle University press release: A gene mutation for excessive alcohol drinking found - VM). They showed that mice with a mutation in the Gabrb1 gene exhibit a very strong craving for alcohol. And then we looked at what kind of changes this mutation causes.
The Gabrb1 gene encodes a protein – the beta subunit of the gamma-aminobutyric acid (GABA) receptor. GABA is the most important inhibitory neurotransmitter, its role is to inhibit nerve signals in the brain. Actually, scientists have long associated the GABA system with the formation of dependencies, which is why they paid attention to it.
For the purity of the experiment, biologists took not just mice, but a genetic line of laboratory mice that, as they say, could not stand alcohol. Because there are other lines of mice that like alcohol very much, especially sweet. In these genetic "teetotallers" they received a mutation of the Gabrb1 gene with the use of a chemical stimulator of mutagenesis. However, it is argued that in natural conditions such mutations occur spontaneously. First, we obtained a whole range of mutations, selected among them those that changed the structure of the GABA receptor, and then selected the one that most strongly changed the alcoholic behavior of mice.
Absolute teetotallers have become binge drinkers. If they were offered a choice of water and a 10% solution of ethyl alcohol, they preferred alcohol. Over time, it began to account for up to 85% of all liquid consumed by them per day.
The experimenters sweetened the alcohol solution with sucrose or not sweetened it and made sure that the desire for alcohol in mice was formed independently of sucrose.
The craving for alcohol was even more convincingly manifested in another test – for self-induction. By pressing the lever, the mice injected themselves with an alcohol solution directly into the vein.
Mutant mice worked the lever so hard that they drank themselves to alcohol intoxication. Drunk mice lost coordination and had difficulty moving.
Alcohol dependence is evidenced by the fact that the mice continued to press the lever in the absence of reinforcement (alcohol), whereas usually this reflex fades without reinforcement.
Then scientists began to understand how the mutation spoils the receptor and what follows from this. They found out that the replacement of one base pair in the Gabrb1 gene leads to the fact that the GABA receptor begins to activate spontaneously even when GABA itself was absent. Since the GABA receptor is an ion channel (a protein that passes ions through the membrane), this channel opened spontaneously, passing ions.
These changes were especially pronounced in the nucleus accumbens, which serves as an essential element in the control of emotions and in the brain reward system. As a result, there was a constant current flowing through the neurons in this area of the brain.
As Quentin Onsti, co-author of the study from the University of Newcastle, explains, "the beta-1 mutation alters the structure of the receptor and creates spontaneous electrical activity in the brain's "pleasure zone", in the nucleus accumbens." "As the electrical signal from these receptors increases, the urge to drink becomes so strong that the mouse is ready to work hard to get alcohol," the scientist said.
The work was carried out as part of a 10-year project to find the "genes of alcoholism" under the leadership of Professor Thomas from Imperial College London. Employees of four other universities are involved in it: the University of Newcastle, the University of Sussex, University College London and the University of Dundee.
"We know from previous studies that the GABA system in humans is involved in controlling alcohol consumption," says Professor Howard Thomas. – Our work on mice has shown that a certain subunit of the GABA receptor plays a key role in this. This is important because it gives hope that we will be able to influence this process – first in mice, then in humans."
About how this gene is the case in humans, "The newspaper.Ru" said Svetlana Borinskaya, a leading researcher at the Institute of General Genetics of the Russian Academy of Sciences.
– Is a similar gene associated with alcoholism in a person?
– In humans, there are two groups of genes associated with the risk of alcoholism. The first group is the genes of alcohol metabolism: alcohol dehydrogenase and aldehyde dehydrogenase. And the other group is the genes involved in the positive reinforcement system, involved in the transmission of nerve impulses in the brain, in the formation of nerve connections.
Currently, there are several dozen such genes in the list of potential candidates for the risk of developing alcoholism. And the GABA receptor gene is in the forefront there, it has now been clearly shown that it is involved in the formation of alcohol dependence, and possibly other types of addictions.
Changes in the work of GABA receptors in some people affect the electroencephalogram. The EEG returns to normal when a person has drunk, and in a sober state he has such a "storm in the brain" occurs. But he drank – and he feels good, brain rhythms are synchronized.
If mutant mice have the same "brain storm" and they do not find a place for themselves without alcohol, it can be harmful to life, and such mutations in the population should be swept out by selection.
In principle, if the mechanism is open, it is necessary to look for analogues of these mutations in humans and see to what extent they manifest themselves. Perhaps the presence of these mutations in humans is incompatible with life in society.
– If we talk about the possible correction of predisposition to alcoholism, can we influence only external conditions or use the products of genes?
– Now research is underway all over the world to understand the molecular pathways of alcoholism, as well as other diseases. To understand exactly which biochemical links are broken in people who develop alcoholism. To select these links as a target for drug development.
And for the treatment of alcoholism, several such drugs are being developed, aimed specifically at those links that are broken. But, of course, normal "external conditions", that is, raising children, normal living conditions, no drugs can replace, but they can reduce the risk or mitigate the manifestation of the disease that has arisen due to a combination of special gene variants and poor conditions.
Portal "Eternal youth" http://vechnayamolodost.ru27.11.2013