Neurotransmitters, part 2

Adenosine, acetylcholine, glutamate and gamma-aminobutyric acid

Atlas, Geektimes

Atlas devoted the first part of the story about neurotransmitters to youth dopamine, norepinephrine and serotonin. In the second post, we will talk about lesser-known mediators who perform important invisible work: stimulate and inhibit other neurotransmitters, help us learn and remember.

Acetylcholine

This is the first neurotransmitter that scientists have discovered. It is responsible for the transmission of impulses by motor neurons – and therefore for all human movements. In the central nervous system, the neurotransmitter takes on stabilizing functions: it takes the brain out of a state of rest when it is necessary to act, and vice versa, it slows down the transmission of impulses when it is necessary to concentrate. Two types of receptors help him in this – accelerating nicotine and inhibiting muscarinic.

Acetylcholine plays an important role in learning and memory formation. This requires both the ability to focus attention (and slow down the transmission of distracting impulses), and the ability to switch from one subject to another (and accelerate the reaction). Active brain activity, for example, when preparing for an exam or an annual report, leads to an increase in acetylcholine levels. If the brain is inactive for a long time, a special enzyme acetylcholinesterase destroys the mediator, and the action of acetylcholine weakens. Ideal for studying, acetylcholine will be a bad helper in stressful situations: it is a mediator of reflection, but not decisive action.

An overabundance of acetylcholine in the body causes spasm of all muscles, convulsions and respiratory arrest – this is the effect that some nerve gases are designed for. Lack of acetylcholine leads to the development of Alzheimer's disease and other types of senile dementia. As a maintenance therapy, patients are prescribed a drug that blocks the destruction of acetylcholine – an acetylcholinesterase inhibitor.

The CHRNA3 gene encodes the nicotine acetylcholine receptor, which can be affected by nicotine. At the first stage, the substance acts on the sympathetic system of the body, which is responsible for spasm of smooth muscles and vasoconstriction. Therefore, for novice smokers, cigarettes cause nausea and pallor of the skin rather than delight. But over time, nicotine reaches brain cells and activates acetylcholine receptors. Since both nicotine and acetylcholine do this at the same time, the brain tries to correct the "double feed", and after a while the neurons of the brain reduce the normal production of acetylcholine. From now on, the smoker will need nicotine for every occasion – in the morning to cheer up, after the meeting, on the contrary, to calm down, after lunch – to think at least a little about the eternal.

The polymorphism of the CHRNA3 gene affects the rate of formation of nicotine addiction and, as a consequence, the risk of lung cancer caused by smoking.

Adenosine

All chemical reactions in the body require energy expenditure. An adenine molecule with several phosphoric acid bases is used as currency in this process. Immediately after the "salary" you will have "three hundred rubles" on your card – an adenosine triphosphate molecule with three phosphoric acid residues. Each transaction costs one hundred rubles, respectively, after the first "purchase", only two hundred rubles (adenosine diphosphate) will remain on the account, after the second – one hundred rubles (adenosine monophosphate), after the third – zero rubles.

A bill of zero rubles is adenosine. As a neurotransmitter, it is responsible for feeling tired and falling asleep. During sleep, zero-zero rubles bills are completed with triples, adenosine is transformed into adenosine triphosphate, and we are ready to return to work with renewed vigor.

There is a way to deceive the "banking system": block the adenosine receptors and go on credit. This is exactly what caffeine does – it allows you to ignore fatigue and continue working. At the same time, it does not bring real energy, but only gives you money to spend, as if you still have three hundred rubles. As with any loan, you have to pay for overspending – more fatigue, attention retardation, addiction. Nevertheless, caffeinated coffee, tea and chocolate are the most popular stimulant in the world.

There are four known types of adenosine receptors that are activated and blocked by adenosine. The ADORA2A gene encodes adenosine receptors of the second type, which are involved in the activation of anti-inflammatory processes, the formation of an immune response, the regulation of pain and sleep. The speed of the body's reaction to injury and trauma depends on the work of this receptor.

Glutamate

Glutamic acid in the form of glutamate is a food amino acid that is found in animal products. Taste buds perceive glutamate as an indicator of protein food – which means nutritious and useful – and leave a note that it was delicious, and it must be repeated. In the twentieth century, Japanese scientists found out the principle of perception of this taste (they called it "umami" – delicious), and over time, sodium glutamate became a popular dietary supplement. It is thanks to him that it is sometimes difficult to resist the temptation to eat doshirak noodles. As a dietary supplement, glutamate does not directly affect the work of neurons, so its "overdose" in the worst case will cost a headache.

Glutamate is not only a dietary amino acid, but also an important neurotransmitter, whose receptors are present in 40% of brain neurons. It does not have its own "semantic load", but only accelerates the signal transmission by other receptors – dopamine, noradrenaline, serotonin, etc. This function allows glutamate to form synaptic plasticity – the ability of synapses to regulate their activity depending on the reaction of postsynaptic receptors. This mechanism underlies the learning process and the work of memory.

A decrease in glutamate activity leads to lethargy and apathy. An overabundance leads to "overstrain" of nerve cells and even their death, as if the electrical network was given a greater load than it is able to withstand. "Burnout" of neurons – excitotoxicity – is observed after epilepsy attacks and in neurodegenerative diseases.

Two groups of genes encode glutamate transporter proteins. The genes of the EAAT group are responsible for sodium-dependent proteins – the ones that are involved in the memorization process. Mutations in the genes of this group increase the risk of stroke, Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis. Mutations in the genes of vesicular transporter proteins of the VGLUT group are associated with the risk of schizophrenia.

Gamma-aminobutyric acid

Each yin has its own yang, and glutamate has its eternal opponent, with whom it is nevertheless inextricably linked. We are talking about the main inhibitory neurotransmitter – gamma-aminobutyric acid (GABA or GABA). Just like glutamate, GABA does not introduce new colors into the palette of brain activity, but only regulates the activity of other neurons. Just like glutamate, GABA has covered about 40% of the neurons of the brain with a network of its receptors. Both glutamate and GABA are synthesized from glutamic acid and are essentially extensions of each other.

To describe the effect of GABA, the saying "you drive more quietly – you will go further" is ideal: the inhibitory effect of the mediator allows you to concentrate better. GABA reduces the activity of a variety of neurons, including those associated with a sense of fear or anxiety and distracting from the main task. A high concentration of GABA ensures calmness and concentration. A decrease in the concentration of GABA and an imbalance in the eternal resistance with glutamate leads to attention deficit disorder (ADHD). Walking, yoga, and meditation are good for increasing GABA levels, and most stimulants are good for reducing it.

Gamma-aminobutyric acid has two types of receptors – rapid-response GABA-A and slower-acting GABA-B. The GABRG2 gene encodes the GABA-A receptor protein, which dramatically reduces the rate of transmission of impulses in the brain. Mutations in the gene are associated with epilepsy and febrile seizures, which can occur at high temperatures.

If dopamine, serotonin and norepinephrine are Hollywood actors of the large neural film industry, then the heroes of the second part of the story about neurotransmitters rather work behind the scenes. But without their inconspicuous contribution, a big movie would be completely different.

In the next part, Atlas will talk about peptides and opioids – this topic requires a separate conversation.

Portal "Eternal youth" http://vechnayamolodost.ru  04.10.2016