GABA or Gamma-Aminobutyric acid is the worst enemy, the ideological opponent of the main excitatory neurotransmitter - Glutamate, which we talked about earlier. The confrontation between them is not like the confrontation between predator and prey, but rather predator and predator, like the Cold War between the USSR and the USA, taking place in our brain. Each has its own pros and cons; there is no good neurotransmitter, just as there is no bad one. Each is beneficial, under certain circumstances. If you haven’t read the article about Glutamate, do so so that your knowledge complements each other.
How does it work
- GABA slows down signaling in adult neurons, and stimulates it in young, developing brains (https://www.ncbi.nlm.nih.gov/pubmed/18500393). This little-known fact, which scientists are still arguing about, tells us about the possible plasticity, flexibility, and individual approach of this neurotransmitter.
- Increases Growth Hormone (https://www.ncbi.nlm.nih.gov/pubmed/18091016). There were many questions on this point after the story about phenibut. Let's go into a little more detail. 11 men aged 18-30 years took either a 3 g GABA supplement or a placebo. Then they either trained or rested. Changes were monitored through blood tests every 15 after administration.
Results: within an hour after administration, the concentration of growth hormone increased by 200-400%.
Another study suggests a parallel increase in prolactin in some people, in addition to growth hormone (https://www.ncbi.nlm.nih.gov/pubmed/7376786).
- GABA increases the brain's utilization of glucose and improves blood circulation in brain tissue. These parameters can be included in the concept of a “healthy brain.” Poor blood circulation is a problem in modern society; gamma-aminobutyric acid partly solves this problem. You won’t be able to immediately count huge numbers in your head, but your “brain settings” will be fine.
- Promotes better sleep and has a nootropic and anticonvulsant effect. GABA has been used in medicine since the 60s and these effects have been tested/retested for years.
Biological activity
In the nervous system
γ-Aminobutyric acid functions in the body as an inhibitory mediator of the central nervous system. When GABA is released into the synaptic cleft, the ion channels of GABAA and GABAC receptors are activated, leading to inhibition of the nerve impulse. GABA receptor ligands are considered as potential agents for the treatment of various mental and central nervous system disorders, which include Parkinson’s and Alzheimer’s diseases, sleep disorders (insomnia, narcolepsy), and epilepsy.
It has been established that GABA is the main neurotransmitter involved in the processes of central inhibition.
Under the influence of GABA, the energy processes of the brain are also activated, the respiratory activity of tissues increases, the utilization of glucose by the brain improves, and blood supply improves.
The action of GABA in the central nervous system is carried out through its interaction with specific GABAergic receptors, which have recently been divided into GABAA and GABAB receptors, etc. They play a significant role in the mechanism of action of a number of central neurotropic substances (hypnotics, anticonvulsants, convulsants, etc.) agonistic or antagonistic interaction with GABA receptors. Benzodiazepines potentiate the effects of GABA.
The presence of GABA in the central nervous system was discovered in the mid-1950s, and its synthesis was carried out in 1963 (Krnjević K., Phyllis JW[2][3]). In the late 1960s, under the name “Gammalon”, GABA was proposed for use as a medicine abroad, then under the name “Aminalon” - in Russia.
According to experimental data, GABA, when introduced into the body, poorly penetrates the blood-brain barrier, but there is evidence that GABA is transported to the brain using specific membrane transporters GAT2 and BGT-1[4].
Beyond the Nervous System
In 2007, the GABAergic system in the epithelium of the respiratory tract was first described. The system is activated by allergens and may play a role in the mechanisms of asthma[5].
Another GABAergic system has been described in the testes and may influence the functioning of Leydig cells[6].
Researchers at St. Michael, Toronto, Canada, found in July 2011 that GABA plays a role in preventing and possibly reversing diabetes in mice[7].
GABA receptors
At the moment, in biology there are only 2 types of receptors: GABA A and GABA B. In the Russian-language Wikipedia, another 3rd type is indicated - GABA C. This was previously thought because there were GABA receptors that were immune to benzodiazipines and barbiturates (classes of antidepressants and sedatives drugs), and since they are immune, it means it will be GABA C. Now such receptors are still classified as GABA A.
GABA - description and functions
Receptors for GABA are located in different areas of the brain: the cortex and basal ganglia. The cortex is the level of the brain associated with seizures, so anticonvulsants activate the neurotransmitter GABA, which begins to suppress the excessive excitability of neurons, which, in turn, arises as a result of the action of another neurotransmitter - glutamate. But the cortex does not work separately from other parts of the brain, and by interacting with them, it controls how we think, move, feel, perceive, learn and act. GABA is responsible for transmitting signals between the cortex and other parts of the brain in order to move muscle groups or stop them.
When the level of GABA is normal, it relaxes the muscles, and we feel not only a decrease in tension, but also an increase in the smoothness of movements and better motor control.
GABA plays a critical role in the development of cells of the central nervous system - neurons. Differentiation of cells into the required number of neurons for the brain occurs due to the presence of gamma-aminobutyric acid. When GABA molecules interact with its two receptors, GABA-A and GABA-B, the position of atoms in the molecule changes, which in turn releases peptides and chemokines that suppress the excitability of brain cells.
And here you may ask - what is so important here?
The fact is that, depending on the activity of different parts of the brain, the excitability of neurons can lead to convulsions, headaches, seizures, anxiety, insomnia, tics and mental disorders. There are many reasons for increased neuronal activity, but the main cause in cases of mental dysfunction is either decreased GABA levels or increased glutamate levels.
Maintaining a balance between these two neurotransmitters is key to our health and well-being. Low levels of GABA lead to the development of anxiety, depression, and impair concentration and attention.
Due to their effect on gamma-aminobutyric acid levels, anticonvulsants stabilize emotions and may help those who suffer from mood swings.
GABA A
Receptors on the surface of nerve cells with which molecules of the neurotransmitter GABA interact. That is, there is one molecule, but it can attach to two types of receptors. The first is GABA A.
Ionotropic receptor, similar to ionotropic glutamate receptors. The action is the opposite. Let us recall that ionotropic receptors are activated literally for milliseconds, at a high frequency of such impulses. GABA acts on this receptor in such a way that it begins to exchange microelements, some leave the neuron, others enter. The result is a change in potential, in this case, suppression of impulses. Thus, the rate of information exchange between nerve cells decreases. On the one hand, this is bad, because a person thinks “slower”; on the other hand, the likelihood of mistakes decreases.
GABA A has sedative, hypnotic, and euphoric effects. By the way, fly agarics produce muscimol, a psychoactive component that works with the GABA A receptor.
There is another interesting substance that has a nootropic effect - xenon. Probably, many people know that there are xenon lamps and headlights in cars, but there is also xenon therapy (a mixture of xenon and oxygen), which activates these receptors and is actively used in sports to release erythropoietin by the body, and this is the main doping of all athletes where endurance is important. This was a small digression)
GABA B
The second type of receptor for our current neurotransmitter and substance is metabotropic. If the ionotropic one worked quickly and often, then the metabotropic one does not change the cell potential, but interacts with certain proteins inside the cell, called G-proteins. A complex biochemical process occurs, the result of which is a change in the conduction of the nerve impulse. GABA B has a long-lasting, growing effect.
This receptor is activated by many drugs, even stimulants (https://www.ncbi.nlm.nih.gov/pubmed/20655488). Its insufficient activation leads to schizophrenia and depression (https://www.ncbi.nlm.nih.gov/pubmed/21303731). It weakens adenylate cyclacyl, to put it simply, there will be less energy and is capable of being an analgesic to some extent (https://www.ncbi.nlm.nih.gov/pubmed/15140638).
Result:
— Gamma-Aminobutyric acid is responsible for calm and tranquility.
- This acid is the complete opposite of Glutamate, although they are both created from Glutamic acid.
- With Glutamate they act by a negative feedback mechanism. When there is more of one substance, there is immediately less of the other.
The substance can be extremely useful and extremely harmful, depending on the timing of administration, purposes and dosages. Remember this often! Good luck!
Functions of gamma-aminobutyric acid
Reduced anxiety and improved mood
One of the main tasks of GABA is to reduce the excitability of nerve cells, resulting in a reduction in the frequency of feelings of fear and anxiety.
There is clinical evidence indicating a connection between a lack of gamma-aminobutyric acid in the body and the occurrence of anxiety disorders.
It enhances the alpha rhythm of the brain, promoting relaxation, improving mood, and smoothing out the effects of stress.
Improves sleep quality
With insomnia, there is a decreased level of GABA. It is noteworthy that in a region of the brain called the thalamus, which is involved in regulating sleep, a large number of receptors for this acid are concentrated. This is explained by the sedative effect it has on the body. When the level is normalized, the speed of falling asleep increases, as well as the time of the deep sleep phase.
Preventing depression
As with insomnia, people experiencing depression are deficient in GABA. After successful treatment, its level increases. Thus, it is used as an alternative to traditional drugs in the treatment of depression and related disorders.
Relieves symptoms of premenstrual syndrome
Premenstrual syndrome (or PMS) is a collection of symptoms that occur before the onset of menstrual bleeding. Typical symptoms: anxiety, insomnia, mood swings, fatigue, abnormal hunger. There is an imbalance in acid levels, which can help alleviate some symptoms.
Relieves pain and reduces inflammation
GABA plays an important role in the transmission of pain impulses and the development of inflammatory processes. Studies note that reduced concentrations of this substance are accompanied by physiological disorders such as fibromyalgia and other pain syndromes. This substance suppresses the transmission of pain impulses and reduces inflammation that is accompanied by pain of various origins. This improves the effectiveness of treatment.
