Hypnotics

Somnologist talks about the therapeutic methods to improve sleep, hypnotics generations and efficacy of medicinal herbs.

It is not always the methods of cognitive-behavioral therapy or use of sleep hygiene can improve the patient's sleep with chronic insomnia. Enhance the effect of these methods is possible while prescribing. It is also possible the use of drugs outside of cognitive-behavioral therapy. We are talking primarily about the sleeping pills, was originally intended to improve sleep.

Barbiturates

For the first generation of sleeping pills include barbituric acid derivatives, the second - benzodiazepines, the third generation - the so-called Z-drugs, which are non-benzodiazepine structure, and the fourth generation - melatonergic drugs. Recently on the market in the US went out hypnotic drug is already the fifth generation - suvoreksant having a completely different mechanism of action compared to all previous drugs. It blocks orexin receptors in specific brain system that is involved in maintaining brain activity and resistance to sleep.

The preparation of barbituric acid was synthesized veronal even Adolf Bayer in 1864. In further studies, it was found that barbiturates have a positive effect on the overall condition of the nervous system, reduce anxiety, seizures affect and promote muscle relaxation. It has also been shown to speed up falling asleep and sleep deepens. Therefore, these products are actively used for the treatment of sleep disorders, and some even being actively used sleeping pills also are composed of barbituric acid. For example, "Valocordin" at high doses contains enough barbituric acid. Or drug "Reladorm", which is half cyclobarbital.

But drugs barbituric acid had a lot of shortcomings, since in their application alters the normal sleep pattern. Indeed, they allow a person to fall asleep faster, but this dream was defective, because the vast stage of deep REM sleep, there was only "average" sleep - the second stage. And also suppresses REM sleep - dreaming. That is, over time people began to sleep longer, but the quality of his sleep suffered and did not give him the satisfaction.

Benzodiazepines

In 1955, that is actually 100 years after the first barbiturate, was synthesized the first benzodiazepine drug chlordiazepoxide structure. These drugs have less side effects compared to barbiturates, although comparable had positive effects. The same applies to sleep: benzodiazepines accelerated the sleep time, sleep time, elongation and reduction of the number of awakenings.

However, it soon became clear that benzodiazepines still suppress deep sleep stage and sleep with dreams, though not to the same extent as preparations barbituric acid. Another important advantage of benzodiazepine drugs for use as a hypnotic was that many of them have a short enough half-life compared to barbiturates. They had time to almost completely withdraw from the body in the morning, when the man of their sedative effect becomes unnecessary.

All barbituric acid preparations have a very long half-life - to several days. And so the man who took barbiturates to sleep, morning, afternoon and evening will be even more to feel its effects, since this drug is metabolized very slowly in the body. Therefore, a more comfortable benzodiazepines have been actively used in the treatment of sleep disorders and is used to this day.

Z-drugs

They were replaced by a new generation hypnotics - the so-called Z-drugs. They are called so unusual, because in fact in the pharmaceutical market there are only three types of sleeping pills, and all their names start with the letter s "Zolpidem", "Zopiclone", "Zaleplon".

At Z-drugs were a lot of advantages in comparison with classical benzodiazepines. It has been shown that they have no such effect on the structure of sleep, especially not suppress deep sleep. At the same time they provide and the acceleration of falling asleep, and sleep time extension. That is, the Z-drugs have a positive effect on the quantitative indices of sleep, while not degrade the quality. These drugs have less potential for the development of habituation and addiction than older benzodiazepine drugs, especially barbiturates. At Z-drugs was also a smaller half-life: they have time to withdraw from the body until the morning, that man did not feel the effects of their reception during office hours.

Z-drugs are fundamentally different in the chemical structure of the substance. Each of them has a unique structure, but combines them that they act on a particular area so-called the GABA A receptor complex which is responsible for the induction of sleep. This drugs act only on the receptor site that is "responsible" for the dream - the alpha-1 subunit - and no effect on the neighboring responsible for the other effects on the nervous system. Benzodiazepines and barbiturates problem was that they were "beaten on the areas" and stimulated once all subtypes of GABA receptors - those responsible for the hypnotic effect, sedative, anxiolytic, anticonvulsant, and amnestic effects of these drugs. Upon receipt of drugs past generations often happens that a man who had "only" to sleep, in addition received another antiepileptic, amnestic and any other action that was quite undesirable. This therapeutic redundancy present in a barbiturate and benzodiazepine drugs.

Gamma-aminobutyric acid is a universal brake neurotransmitter of the central nervous system. In conjunction with the specific receptor of the GABA in nerve cell increases hole size - a channel through which penetrate into negatively charged chloride ions. The more cells accumulate these ions, the less it reacts to other influences - it is said to be inhibited.

Z-drugs were more pure, having the minimum number of unwanted side effects than benzodiazepine and barbituric drugs, so they very quickly began to be used as hypnotics. They are called non-benzodiazepine hypnotics, because the name "benzodiazepines" due to the peculiarities of the chemical structure of the previous generation products. They all must have two rings - benzene and diazepine. Z-drugs of the formula in its rings do not have. Nevertheless they bind almost the same areas of the GABAA receptor as benzodiazepine drugs.

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Melatonin and Insomnia

Hypnotics fourth generation are associated with fundamentally different types of receptors - receptors for melatonin. Melatonin is a rather mysterious substance. This hormone, which is released only at night. When the night is reduced light intensity, in animals and humans begins to produce the substance. It is believed that one of the most important action of melatonin blockade is the antioxidant and reproductive function. One of the adverse biological effects of this hormone is to accelerate the onset of sleep. It also affects the internal clock of our body that are responsible for translating it in day or night mode. Depending on time of day is dark or light, the body by increasing the production of melatonin gives a signal to the internal clock that it is time to activate the nervous system or, on the contrary, slow down. That is Melatonin promotes sleep onset is not a sleeping pill now, and by switching the internal clock in the night mode.

The latter, at least currently available hypnotic drug, which in 2014 was approved for use in the United States, is suvoreksant. The action of this drug is also based on a fundamentally different from the previous four generations of sleeping pills mechanism of action - blockade of one of the brain activates the system. Along with many others there are two main systems providing the level of functioning in the brain - activating and inhibitory.

In the daytime dominated by activating the system. They keep the brain awake, provide a sufficient level of attention and readiness for action (alertness). When the evening light output is reduced, accumulated so-called fatigue, increases the so-called "sleep pressure", it is already beginning to dominate the braking system. Their activity overcomes activating activity centers, and the brain is immersed in the dream state. By activating brain systems - and there are described twelve - and carry a very important, powerful system - the so-called orexin. In this system, the brain centers there is another name – Hypocretine. Scientists can not yet determine how to properly call the mediator, who is a carrier of information in the system, either hypocretin or orexin. Because the system was simultaneously described by two groups of authors who discovered the substance and named it accordingly hypocretin and orexin. No one wants to give the championship title. So through slash and is usually called the mediator - orexin / hypocretin.

It turned out orexin system is very important to maintain the level of wakefulness. What happens if you turn it off? For a person suffering from insomnia will be able to fall asleep more easily, because the brain is partially activating system "will lose support," on the part of this important and then the braking system of the brain can take advantage and finally immerse the body into sleep.

What other hypnotics other than those listed may be used in the treatment of chronic insomnia and how it justified? Popular is the use of melatonin medications - hypnotics not the fourth generation, which are powerful, specially synthesized agonists of melatonin receptor, and a synthetic analogue of the hormone melatonin. It is shown that the use of these drugs improves a little time to fall asleep and slightly increases the duration of sleep. Most drugs called melatonin hronobioticam. Such a compound word says that the active substance "work" through the internal clock, and not through the system, which regulate the cycle of "sleep - wakefulness." That is, they do not slow down, do not activate, and are the third component of this interaction - on an internal clock, which give the body more clearly understood when the day and when night. Our own hormone melatonin is produced only at night. Accordingly, if we take a tablet of melatonin during the day, then we can try to trick the internal clock that night had fallen and it is necessary to switch the system to night mode, including lower brain activity, which promotes sleep.

So uncomplicated way, of course, switch the nervous system can not sleep. However, it is shown that such assistance braking system through deception of the internal clock allows the bit to increase sleep time and reduce the time to fall asleep. Preparations melatonin is now very popular, widely used - largely due to the fact that their use is almost no side effects. Their great advantage over other sleeping pills is the so-called high safety profile, so they are often prescribed to improve sleep for older people.

"Donormil" and antihistamines

Besides preparations of melatonin as a hypnotic actively using blockers of histamine receptors, ie the means which are commonly used for allergies. Known to all "Diphenhydramine" ( "Diphenhydramine"), "Suprastin" - why these older antihistamines have a sedative effect? Because they block the passing another important brain activating system - histaminergic. This system also contributes to the brain in awake. If it weaken or off (depending on dose), the "sleepy" system gain an advantage, which is what happens when we take nonselective antihistamines older generations. This feature uses a more modern drug with hypnotic effect, which is called "doxylamine," - he selectively blocks the H1-receptor in the brain that are in histaminergic activating system. Due to this, again the opposite side in the form of braking system takes advantage dive brain to sleep.

The drug "doxylamine," the strength hypnotic action is usually weaker than classic sleeping pills. Its advantage is that it is quite accessible, that is to retrieve it using a simple recipe that can prescribe any doctor. This drug may cause side effects, especially in the elderly-related deterioration, such as glaucoma or BPH, but in real life, such side effects occur less frequently. "Donormil" does not distort the structure of sleep as it does with benzodiazepines and barbiturates, that is, allows natural sleep. An interesting feature of this drug is that it is the only sleeping pill approved for use during pregnancy.

This is due to the fact that the drug is used and nausea of pregnancy. It has been shown that the combination of "doxylamine" with vitamin B6 reduces the severity of nausea. In the United States it is actively produced and sold. Therefore, the question of whether you can or can not be removed once the appointment is shown to pregnant women. But to use it while breastfeeding is impossible.

Medicinal herbs

Preparations of medicinal herbs - how they work or do not work for the improvement of sleep? Is it possible to separate the effects of medicinal herbs products from the so-called placebo effect, when a person is waiting for a means to help him, and it helps? With regard to the effects on sleep valerian, Leonurus, chamomile, hops and so on are no placebo-controlled studies have been conducted. That is, we can not say whether these drugs are better than placebo, or to improve sleep, which tell their host people are due simply to the fact that the placebo effect works, and they get the expected.

In meta-analyzes this effect has not been proven. A meta-analysis - a study when the results of all studies taken a certain drug, summarized, processed statistically and the authors look whether there is a shift of the drug effect in a positive way. In most surveys of this kind of positive influence of valerian preparations (Valeriana most studied) in the human sleep metrics were found.

A possible positive effect on sleep herbal medicine preparations explain their sedative (soothing) effect, when reduced levels of internal stress and the person falls asleep easily. However, the placebo can also cause sedation. When a person receives a placebo, if he does not know it consciously or unconsciously expects that it should be easier (reflex). And it is an idea often comes true regardless of whether the person was given a drug or not given. It is shown that much greater effect have a "dummy" larger, red, and in the placebo injections acts more noticeable than in the tablets (no pain - no gain, as they say athletes).

In conclusion, it should be noted that, despite the apparent simplicity of the mechanisms of action of sleeping pills (some act on the braking system, the other - to activate, and others - on the internal clock), their use should be prescribed by a doctor, as a place of use of these funds is still a brain - the main control center of the body - and must be handled very carefully.

5 Movies About Insomnia

Somnologist recommends the best films of mixing dreams and reality, the consequences of insomnia and Combat with it.

Sleep disorders and unusual dreams are a popular means of displaying movies inner world of the characters and their suffering. Indeed, sleep is very sensitive to psychological ill-being, and the most common of the sleep disorder - insomnia - in 80% of cases, is a manifestation of mild or more severe mental disorders. As for dreams, writers roam in this field according to their conception of Freudian concepts, while in modern psychoanalysis she only pays tribute, and work with the patient is carried out by other, more modern techniques.

Insomnia, 2002 (Director: Christopher Nolan)

The film's title refers directly to the most famous of sleep disorders. Game magnificent duo Al Pacino and Robin Williams is set against the backdrop of the White Nights of Alaska and the remorse of the protagonist, who can not forgive himself for the death of his partner. It seems to reactive depression, insomnia and acts as one of the main symptoms in the face of adverse conditions for sleep.

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El Maquinista, 2004 (Director: Brad Anderson)

There is not just insomnia, but also repression of the memory of what happened with the replacement of their respective environment and appearance of the protagonist, and that gives meaning to all the sinister act. Christian Bale is at a height, or rather, one of his career highs. In clinical terms this film shows PTSD.

Fight Club, 1999 (Director: David Fincher)

Pictures of insomnia in this film is not, but the very appearance of the protagonist in the daytime suggesting harmful effects of insomnia and other excesses. Dump all be accomplished at this film on poor sleep is not: it is not too convincing excuse. But the diagnosis of schizophrenia with multiple personality - a good excuse to escape punishment. Actors need not be mentioned: their names and work in the film and so called breathlessly.

Fear and Loathing in Las Vegas, 1998 (Director: Terry Gilliam)

The specialist can say that this film is about the dangers of the use of psychotropic drugs and related social and biological functioning disorders. "Why disorders?" - Asks a lover. The director took on the task of visualizing sensation arising from these fans, sleep disturbance in this case is used for thickening effect, when the heroes begin to confuse it with reality or experiencing sleepiness during the day from lack of sleep at night. In this state of the International Classification of Sleep Disorders year 2005 is regarded as "insomnia while taking medicines or other substances."

Lost in Translation, 2003 (Director: Sofia Coppola)

Yet there are in the sea and the islet pathology of hope. It is not always pernicious insomnia and hopeless. The heroes of the film - and this is no less than Bill Murray and Scarlett Johansson - back in Tokyo suffer from linguistic isolation and a bit of jet lag (jet lag syndrome). Happy exhausted lack of sleep Bill Murray somehow engaged in productive activities, but the nights are filled with various kinds of leisure in the exotic country. Once this option is a sleep disorder called Edison effect: the widespread introduction of electric lighting led to a restriction of sleep time due to the conversion of the day into the night. Not the bad kind of sleep disorder.

Gamma-aminobutyric acid

Physiologist says the imbalance of excitation and inhibition, benzo-diazepines and barbiturates use in medicine.

An important mediator of central nervous system is gamma-aminobutyric acid (abbreviated - GABA).

This substance is the main brake neurotransmitters of the brain, and is in constant competition with glutamate. Glutamate - is the main excitatory neurotransmitter, and its use as a mediator of approximately 40% of the cells. GABA - the main brake for mediators, and again as a mediator is used about 40% of the cells. This leads to parity and the delicate balance of excitation and inhibition in our brain.

Brake function is tremendously important. It is necessary to block the unnecessary information flows. In the XIX century, at the dawn of the study of the brain, it was believed that the institution holding the information - this is very important, and when the information is not available - it's kind of inhibition. Then it turned out that everything is much more complicated. And braking - is not the absence of excitation, and active process that requires its own nerve cells, synapses own, its own mediators and inhibition of energy, our brain is spending perhaps more than even in the excitement. Because in the brain all the time "wandering" Thousands, hundreds of thousands of information flows, and leave only those that are needed, those that are relevant, very difficult. If you do not remove the excess flow of information, "noise" in our brain, which is already very high (no wonder the brain called the noisy computer), simply everything to score, and thought that you started to think, and not come to a logical conclusion.

Therefore, GABA - is a very important mediator. And it is linked to functions such as attention, that is, setting a certain flow of information, motor control, emotional control. At a time when, for example, a first grader decides that he must sit quietly at his desk, unable to move and listen to the teacher, the neurons in his brain, especially, say, in the thalamus, a large amount of secrete GABA, and, indeed, the extra information threads are blocked. And just to sit quietly and not move - it is a huge burden on the GABAergic nerve cells.

GABA - is a fairly simple molecule, resulting, paradoxically, of glutamate. Such is the chemistry of our brains that the principal obstacle to the mediator is the product of a small fracture of the main exciting mediator. That is cleaved from the glutamate carbon dioxide, and has been turned gamma-aminobutyric acid, which can further be used as a mediator and is synthesized in a place right in the synapses. GABA - is not an amino acid food. We do not eat it, that is, it is obtained by synthetic processes in different our cells, primarily in neuronal cells. I must say that in GABA neurons performs two very different functions. Approximately 1% of the substance acts as a mediator, and 99% or perhaps even longer work in the mitochondria during energy exchange, during ATP synthesis and breakdown of glucose. This path - the path decomposition of glucose - is characteristic for neurons. That is, it is not very noticeable in other cells. In nerve cells when glucose falls, one of the intermediate products - it is just the gamma-aminobutyric acid. And at the time for a long time could not believe it, just as in the case of glutamate, that the substance is a mediator, because it is very much in the brain. That is, it would seem, the mediator also has a very delicate function, it should be small and only in the synapses, and here we see that a lot around the GABA neuron, particularly in mitochondria.

You can find GABA in the following drugs: Pantogam, Picamilon etc.

It was found that GABA dual function, and there are quite interesting consequence of this effect, such a "division of responsibilities". If we begin to use GABA as a drug in pill form (such as a tablet is to say, "Aminalon"), is getting into the brain, GABA is not very good, but it passes the blood-brain barrier and enters the nervous system. Once in the brain, neuron, this gamma-aminobutyric acid is not so much an additional brake mediator, who came from the outside, as a good "food." These molecules are captured GABA primarily mitochondria, oxidized, and get extra energy. That is to introduce GABA - is to feed neurons. Thus tablets the gamma-aminobutyric acid performs the function of the overall strengthening of the nervous system, improve. This is especially true of higher brain functions such as thinking, perception, attention.

this kind of drugs called nootropics - a special term coined ( "NOE" - this 'knowledge', Vernadsky, for example, wrote about the noosphere). Nootropics - are drugs that improve the higher functions of the human brain. And they, of course, very, very much in demand, are used in the case of a brain injury, stroke, or any changes or age, for example, when the brain matures too slow or very tired. Suffice it to a wide range of applications. But it is important to distinguish from other nootropics drugs, such as psychomotor stimulants. Sometimes the substance activates the synapses, issue of nootropics. In fact, the real impact is nootropics metabolism in neurons and some synaptic processes impact almost no effect. For example, the present nootropics improve energy generation in mitochondria ameliorate neuronal membranes, improve protein metabolism and so on. If nootrop positioned as a substance having the synaptic activity and acting, for example, nicotinic receptors at dopamine receptors, it is not nootrop. Such a substance should be taken seriously since, with caution because any preparation, real influence on the operation of synapses may cause addiction and dependency, so it's actually not easy. GABA, such as "Aminalon" - this is the true nootrop because the inhibitory effect on the nervous system has practically none.

To gamma-aminobutyric acid is operated as a neurotransmitter, it must be formed in the presynaptic end, the end of the axon, respectively, of glutamate. Then it is released when the nerve impulse comes, and acts on receptors. By the described two types of GABA receptors, which are called the GABAA receptors and GABAB receptors. Both are sure to cause inhibition. That is, gamma-aminobutyric acid - a mediator, always causing braking. That is, it has a definite effect - the cessation of information flows. In reality, this means that there are a large number of synapses in the nerve cell membrane - in some of them is, for example, glutamate, the signal is carried out, but GABA is released here, and if GABA stood out, it can block the holding of these signals. For example, you see orange, and still you'd like to have - two exciting channel that should run your reaction grasping orange and immediate zapihivaniya it into his mouth. But if there is a synapse, where stands of GABA, it can inhibit the inclusion reaction and GABA isolation may mean that it is not your orange, it lies on the tray in the store and you it is not bought, so no need to grab and shove in your mouth.

Impact Brake mediators, which limits our responses, motor, emotional - it really is a very important component of our behavior. That is, the effect of GABA allows to control a variety of reactions, and, accordingly, if there is no GABA if synapses are not active enough, then there is an imbalance of excitation and inhibition. In general, these situations of imbalance of excitation and inhibition frequently inherent in different manifestations of nervous activity. The easy option arises, for example, increased anxiety, impulsivity, in more severe cases, such as insomnia. In children, it is observed as attention deficit hyperactivity disorder: not enough attention and too many motor reactions, difficult to sit at a desk and do nothing. And finally, the most difficult situation, when hit by a very strong balance sheet - it is epilepsy. Epilepsy - is a classic neurological disease in which a certain area of the brain, usually local, so much excitement that this zone periodically erupt activation waves, causing a seizure. And if we want to somehow deal with it, we must first strengthen the work of the GABA system and use drugs that GABA A receptors and GABA B receptors are forced to actively operate. If we use a substance hindering work GABAA receptors, we can, for example, experimental animal or cause increased anxiety run seizures. This is also used, for example, to study the genesis of epilepsy and further select drugs.

It must be said that the evolution of plants has created a lot of toxins, tripping GABA receptors. Known, for example, or bikukulin picrotoxin - these substances by themselves are very powerful convulsive drugs and plants using this type of toxins, poisons protected from herbivores. Sometimes it is quite harmless-looking grass in their sheets of paper contains a hellish poison that at very high dilution can become a drug activates the little brain.

Accordingly, if we want to restore the balance of excitation and inhibition and activating the GABA synapses, GABA receptors, we need substances like gamma-aminobutyric acid. Chemists have found these substances in the late XIX century. At that time, nothing was known about GABA or even synapses. Just going through the various options, accidentally came upon these compounds. The first group of these drugs, "barbiturates" was named. Barbiturates were discovered by German chemists in the Day of Saint Barbara. Varvara (Barbara) - hence the name "barbiturates". However, there is a second root - "urate", which means 'uric acid'. According to one legend, the substance was isolated from the urine on the day of St. Barbara, hence a German romantic name. Barbiturates used in medicine for a long time and are characterized in that cause total inhibition of the brain: the movements and emotions, and attention. Phenobarbital is a part of quite ordinary products, which even sometimes sold without prescriptions. Say, "Corvalol" calms the heart, but one of its components - is phenobarbital, very calming brain, and if you take too much dripped drops, then you have a deceleration of emotions, thought processes, and it is quite dangerous for those who, for example, He is sitting behind the wheel, because the reaction rate decreases. Therefore, barbiturates always very organized pharmacologists, there was a search softer active compounds. By the middle of the XX century there were compounds such as benzodiazepines. They already operate more smoothly and is now used as anti-anxiety drugs, tranquilizers. They are used in epilepsy, in order to reduce the likelihood of seizures. A barbiturates continue to be used for anesthesia, because, when the operation is a long time, it is more suitable barbiturates.

And another group of drugs related to gamma-aminobutyric acid - valproate is. The fact is that when the gamma-aminobutyric acid has fulfilled its function and gave a brake signal on its need to destroy. It makes a special enzyme, called GABA-transferase, and valproate - a blocker of the GABA-transferase. And if we use, we achieve the effect as long floats in GABA synaptic environment longer acts on receptors, respectively, also enhanced the inhibition in the brain. And valproate are very important drugs for epilepsy, because they can be used chronically, gently, in small doses. And they are particularly relevant with childhood epilepsy, when you need to carefully monitor the state of the child's nervous system and very accurately pick up doses, depending on its age.

Why do people cry?

Physiologist talks about the difference between tearing and crying, stress hormones and mechanisms of allocation of tears.

In order to answer this question, we need to distinguish between two concepts: tearing and crying. Lacrimal fluid is produced constantly and helps protect, wetting and nutrition eye tissues, because the cornea is not the most blood vessels capable of providing its food. Increased lacrimation - a protective reaction of the organism to external stimuli, the action of which is allocated tear fluid, which provides additional protection for the eyes. The tear, as well as in saliva contains lysozyme, which has an antimicrobial effect. Tearing may also occur when yawning, action pungent smells, odors such as onions or peppers. When these stimuli triggers a special protective reflex, similar to those that occur when a person hit or pricked. Reflex tearing at irritation of the mucous membranes occurs due to excitation of receptors sensitive fibers branches of the fifth cranial nerve - the trigeminal nerve. This tearing may also occur in some species.

Mechanisms for allocation of tears when crying differ from tearing mechanisms. Lamentations - is primarily an emotional response inherent to man. Most often, people are crying, experiencing negative emotions, but strong and positive emotions can also cause crying. In this case, the secretion of tears is provided by the emotion-the limbic system of the brain. The command is transmitted to the lacrimal gland due to the parasympathetic division of the autonomic nervous system, which is due to the release of acetylcholine, a neurotransmitter of the parasympathetic system, increases the secretion of tear fluid. Isolation tears during emotional arousal - grief, sorrow, religious feelings - is provided participation of the limbic structures that control various autonomic functions of the body - the hippocampus, septum, hypothalamus.

Limbic structures of the brain are signaling the facial nerve - the seventh pair of cranial nerves. Thus, innervation and increased secretion of tears mediated by parasympathetic fibers of the seventh cranial nerve. The parasympathetic nervous system department has a relaxing and calming effect, its activation leads to the restoration of the body after various stresses. So people say that a small tear heals great sorrow. Increased parasympathetic system relieves the body from stress, excessive stress and promotes sleep. The mechanism of allocating tears of joy is the same as with sadness: it is provided by the same excitations emotiogenic brain structures.

It is known that in the tear, which is provided emotional arousal structures contain certain hormones such as prolactin, adrenocorticotropic hormone. Adrenocorticotropic hormone stimulates the release of cortisol in the adrenal glands. Cortisol is the main hormone that creates change in the body's functions under different stresses. Prolactin is also considered one of the stress hormones. Like other peptide hormones, it has a broad effect on the different organs. In particular, the prolactin increases lactation in the mammary glands, and has analgesic effect. It is believed that it reduces the feeling of pain when biting a child the mother's nipples.

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Also, if weeping in tears of increased hormone content antinociceptive (analgesic) system - enkephalin, which reduces the feeling of pain and an inducer of positive emotional states of euphoria and happiness.

In addition to increasing the secretion of tears, cut certain facial muscles when crying, which lead to the twitch of the lips, nose, to sob, the movements of chewing muscles.

Crying has an important communicative function: it allows you to better communicate to members of the community and understand other people's emotions. For example, in the old days in the Russian villages were even special mourners, who were invited to the funeral to create a general atmosphere of grief and sorrow. For example, thanks to pay the child's mother better understand his condition and needs. It is believed that a child up to 4 months when crying tears were not yet allocated, as special nerve pathways for this has not yet been formed.

5 myths about stress

Experts debunk myths about the nature of stress and how to deal with it. Experts - scientists debunk myths and explains common misconceptions. We asked our experts to comment on popular myths about the factors of stress and counteract it.

A person's reaction to stress is determined by the genes

This is partly true.

Genetic features contribute to how people react to stress, but do not completely define the reaction. Stress response also depends on what exactly caused this stress (response to terrorist attacks more than occurred without malice disaster comparable in scale) on the duration of exposure (acute or chronic stress), from the acquired skills to cope with stress. The genetic component can be divided into two parts. One actually genetic, determined by the characteristics obtained from the parents of genes that control the function of the nervous, endocrine and immune systems. Carriers of certain gene variants are more responsive to stress or slower to return to normal after the reaction, and consequently are more likely to get stress-related disorders. For some of these genes shows the effect of education conditions. In people who have had a happy childhood, and those who grew up in unfavorable conditions, the same gene variants can manifest in different ways.

The second component is determined by the life story, especially experienced in childhood stress. In mammals, there is a special system that adjusts the intensity of the genes under specific environmental conditions. As a result of these systems in the areas of DNA regulating switching on and off the genes appear special chemical tags (methyl groups) that affect how active a gene is. Experiments on mice and rats have shown that experienced in childhood stress alters stress response genes work life. Similar data were obtained for a person, but not as a result of experiments, and in the study of the DNA of children who grew up in favorable and unfavorable conditions. Interestingly, if the mother-rat is a well cared for of stressed pups (carefully combed out and licked them), the number of methyl tags on their DNA returned to normal, and when they grew up, their stress response was not different from the reaction of rats raised in " affluent "families.

Changes in genes work by intravital chemical modification of individual sections of DNA or other impacts studies branch of science called epigenetics. Epigenetic processes - this is what connects the reaction the genetic apparatus in the impact of the environment, including genes and response to maternal love, neglect and other conditions of education. And these conditions are, in turn, although not fully determined but contribute significantly to how a person will react to stress. Therefore, even when we talk about the culture and education of, the phenomena that are far from the genetics, just shrug off the genes can not. It allows you to record the work of genes in the form of nerve connections that which lives and parents teach children.

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Stress is caused only by negative emotions

It is not true.

Stress - a reaction of the body, which says that the body comes from the state of homeostasis, ie the balance.

But out of balance is necessary for life, for a person to develop. Therefore, stress can be a state of love, and a performance in front of a large audience, then there are some things that are quite comparable to the good life. Thus, the stress necessary for life, and it is basically linked to any situation in which we are anxious.

As for the negative emotions, then this case is the concept of "distress", the so-called bad stress when experienced negative emotional states are either very intense or chronic. It differs from the usual stress that a person falls into the external situation, which constantly leads him off balance, and constantly experiencing negative emotions, not from time to time. For example, subjected to harassment at work, or his constant conflicts in the family with his wife, or he does not like his job and every day for a long time have to push yourself in the morning to get out of the house. Also high intensity distress may be due to stress, that is, when negative emotions are too strong. For example, the loss of a loved one, or when there is something very frightening, or when man stands in front of a serious threat. Distress can be really bad influence on mental and physical health, and such stress necessarily requires some intervention, the request for help and so on.

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Food helps to relieve stress

It's true.

We must start with the fact that the stress - this is not always negative emotions, and it may be caused by positive emotions. From the viewpoint of the body and of the internal organs euphoria - is also stress. Therefore, we can, unfortunately, die and joy. This myth concerns the stress that appears on the background of negative emotions. If a person had such stress, it can help all that evokes positive emotions. And the food - the most reliable source of positive. A piece of meat or chocolate you never disappoint. You may not like the concert, you can quarrel with her best friend, but a piece of good food at the right moment ensures positive emotions.

In nerve cells the level of food promotes the release of mediators of positive emotions. Once in the mouth area appear pleasant taste sensation, stomach and starts to fall something in the brain and begin to secrete endorphins dopamine. The result is a positive emotional state that blocks the negative experiences. This mechanism works on the innately specified principles as food - a source of energy and building materials, without which we can not exist. Therefore, evolutionary processes have formed a brain configuration, which provides the power process through hunger forcing us to eat every day. And eating a newborn due to innate reflexes, but later learns very quickly to find food, and training is on the background of positive emotions caused by the absorption of food.

There are people who really overeat from stress. But as a rule, if a person controls his behavior, he is looking for other sources of positive emotions, to relieve stress, which is caused by negative experiences. He can go to the exhibition, to do sports or play a computer game. Eating relieves stress, but it is often used this way should not be, otherwise the consumption of excess calories you face stress already about obesity.

For residents of the metropolis daily stress is inevitable

This is partly true.

This statement is only partially true. Stress - a condition that occurs when the human body exposed to stimuli that are difficult to adapt to it. These incentives can be very different - from loud noises to conflicts with others. we encounter quite often in a big city with such incentives. This is the environmental conditions in which we live (eg, air pollution and loud machinery noise), a large number of people with whom we meet (for example, in a crowded public transport or in a traffic jam), the time limit and the big physical activities, problems in the family and at work. All this can cause stress.

However, there are three limitations to this case. Firstly, there are many stressors people living not only large, but also in small communities. These include, for example, are working conditions that cause a person severe physical fatigue or a feeling of injustice. Secondly, even in large cities, different people are in different conditions: someone sits down in the morning to the old crowded train, and someone in a comfortable express; someone standing in traffic jams, and someone traveling on the open road; someone comes to work as a holiday, and someone wants to leave her forever, and so on. This means that by choosing the way of movement, life partner or a job, we can influence the level of stress.

Finally, thirdly, the impact of many stressors depends on our interpretation of what is happening, our relationship to it. Imagine that two people have to meet the challenge. One person thinks: "Here we go again! I do not know what to do. I can not solve this problem, and I was expelled from work. " In other words, he sees it as a heavy burden, which is able to cause serious trouble. Another person thinks differently: "How interesting! I do not know what to do, but be sure to come up, and I succeed. " He sees this as a challenge that will be able to answer. As a result, stress occurs first user rather than the second. It follows a simple conclusion: yes, the big city throws us constantly stimuli that can cause stress, but we are able to increase or reduce their impact.

Stress can cause real harm to health

Stress can really mobilize the forces of the body, enhance human activity. However, certain kinds of stress, especially due to the influence of intense stressors can adversely affect human health. For example, there are traumatic stress, which has a variety of adverse psychological effects. It is believed that traumatic stress caused by the influence of the stressors of high intensity, which are associated with a risk of human life, and his loved ones. Traumatic stress leads to disruption of the usual functioning of a person. Such stress is dangerous not only to actual manifestations, but also delayed. For example, in post-traumatic stress in a certain part of people who are more vulnerable to stress, there may be consequences in the form of direct experience of this situation, as the six months after the traumatic event, and in a few years or even decades.

If we talk about the impact of the stress on physical health, the effects of stress can be expressed in different ways: violated the normal level of wakefulness, sleep problems, there are somatic reactions such as increased heart rate, breathing and so on. With this stress can also have problems with the gastrointestinal tract, skin diseases, and various other effects.

Of course, wrong to separate the psychological effects of stress and consequences associated with the state of physical health. It has long been established system of human response to the fact of the situation. For example, difficulties with emotion regulation may lead to an increase in waking time, difficulty falling asleep, intermittent sleep, early awakening to chronic. If a person is not getting enough sleep if he is constantly in a state of hypervigilance that is constantly expect some trouble, it can not recover, relax. And here and there are a variety of diseases, especially those in relation to which the person is most sensitive.

But wrong to think that there is only harmful stress, distress. There is another level of stress - eustress. Such manifestations of stress wrote Hans Selye. This favorable stress, in which the mobilized forces of the body and a person comes to tone. And the tone including performs a protective function. For example, when a person needs in some circumstances to avoid undesirable factors or when he really need a certain tone of the state, in order to solve the real problem.

That is, the stress can affect both positively on the human condition, as well as detrimental. It is important to note that this is also connected with the human condition. The fact is that usually a person experiences a variety of stresses and do not always recover quickly after them. Accumulated, the cumulative stress - the result of the experience many negative events in connection with what one person a specific stressful event will have obvious negative consequences, and for the other would be the last straw.

In general, the myth that stress is not harmful to human health, has the right to exist, because by creating a myth, people thus try to convince themselves that there are no problems, to protect against anxiety that arises at the thought of the negative effects of stress man is inclined to deny the problem and how to escape from their fears. In fact, it is illusory salvation. The lack of knowledge about what the effects of stress can be negative, not to protect people from these effects, but on the contrary, disarms him in coping with them. As is known, the denial of the problem does not eliminate it, but, paradoxically, makes it even more difficult to be solved. Courage to admit to himself that after the events of a difficult life and health have changed for the worse, it opens the way for treatment to their own resources or social support, to help other people.

5 myths about the brain

Experts debunk myths about the features of our nervous system. Expert debunks scientific myths and introduces readers to the comments of our experts, who explain common misconceptions. We asked our authors to talk about the reasons for which were formed those or other well-established ideas about the brain.

The brain works by only 10%

It is not true. As we record brain activity, in particular activity of nerve cells, count the number of neurons we can meet when registering with a separate electrode. Knowing the sensitivity of the electrode at which distance it "hears" neurons, and knowing that the active electrode can feel neurons in a certain volume, morphological slices we can establish that a given volume of the brain is for example 1000 cells. But in this case, when the electrode is in the brain, we hear, that the active neuron is very small, just in the area of 5-10% or less.

But this understanding of the brain by mistake, because the registration of these neurons occurs in the moments when the animal or person perform some behavior engaged in some activity. If we are talking about free-rolling animals that are awake and performing some activity, it turns out that in every single activity executed participate, not all neurons, namely a percentage of the total. A person can not simultaneously drive the car, reading a book, playing the piano and skiing. Accordingly, at a time when performing a certain activity, activity logs one neuron to another point - the activity of other neurons, and so on. Thus, registration of a very small percentage involved in some form of neuronal activity does not mean that the brain is not working at 100%, but it works only 10% (in the sense of "bad" works).

Intelligence level depends on the size of the brain

It is not true. It seems that it is very simple: to measure the level of intelligence and brain size and to identify associated with one another or not. But how to measure the level of intelligence? Of course, there are standard tests such as IQ-test that can measure the level of certain mental abilities. But when we talk about intelligence in general, this is not always the ability to solve math problems or rotate some figures in space. Rather, it is the solution of everyday problems or questions, planning, communication and much more. Such capacity in standard tests, which are carried out almost always in writing is quite difficult to identify. So we can not compare the size of the brain and the overall level of intelligence, and we can only talk about the relationship with the results of certain tests. Of course, such studies have been, and indeed most of the studies found a positive correlation. Even in the best cases, the size of the brain explained from 5% to 10% of the test results for intelligence.

In addition, there is an evolutionary aspect. It is believed that during the evolution of the human brain with increased level of intelligence. But if we look at the evolutionary history of our species, we will see that this is not true. The brain of Neanderthals or Homo sapiens, who lived about 100 thousand years ago, was larger than that of modern man, that is, in the last 100 thousand years, the average brain size decreased in humans. Therefore, in the evolutionary process and can not see a direct correlation between the increase in brain size and increase the level of intellectual abilities.

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The brain is a gray substance

It is not true. When we speak of the brain as "gray matter", there is an idea of some kind of a uniform gray mass, unorganized structure, which nevertheless derive the processes associated with the solution of vital issues. Indeed, traditionally customary to speak of "gray matter" (brain areas rich in neuron bodies) and "white matter" (areas rich in myelinated axons). In fact, the structure of the brain is much more complicated.

The brain consists of a plurality of structures, each of which has its own function and thus difficult organized. In Examples include the hippocampus, amygdala, nucleus accumbens, thalamus, and so on. Each structure of the brain is made up of a large number of different cells. They can be divided into neurons and glial cells. By glial cells include astrocytes, microglial cells and oligodendrocytes. Neurons may also differ by type: it may be excitatory glutamatergic neurons are GABAergic inhibitory neurons and so on. This structure as the medial septum, rich in neurons, which as its main neurotransmitter acetylcholine are; other structure - black substance - contains a large number of neurons, the main of which is a neurotransmitter dopamine. Violation of the data types of neurons observed in the development of neurodegenerative diseases such as Alzheimer's and Parkinson's disease.

Nerve cells that constitute the brain structure is formed between a neural network. They communicate via electrical synapses and conduct signals coming from the peripheral structures. These connections are flexible - the efficiency of the electric pulses may increase (in this case we speak of potentiation) or decrease (in this case we speak of depression). The property is plasticity - a fundamental property of the nervous system, which allows it to process, store and reproduce the information. Thus, we can say that the brain is constantly changing structure. It is important to note that the nervous system - the most highly organized system of our body.

The left hemisphere of the brain responsible for rational and the right - for creativity

This is true only in part. One can not say what prevails in the hemisphere rational and creative solving of problems, because it leads to a strong simplification of ideas about how the brain. Incorrectly assume that one hemisphere is responsible for a single process, and the second - for the other, as the entire brain somehow involved in any mental process. However, there are problems in which the solution to a greater extent one hemisphere involved. For example, when solving spatial problems dominant right hemisphere, but also left an important contribution to these processes. If you need to write a summary of its content, you must first understand in which will participate and the right and left hemispheres. But the left hemisphere will be more involved in the drafting of the text.

The distribution of tasks that solve both hemispheres, is not static, it changes with age. Consider it. In adults and newborns in the perception of words is activated by the left hemisphere, the perception of intonation - right. However, in children 10-18 months, it causes activation of both hemispheres, more on the right, and the right hemisphere lesion leads to a more pronounced lag in the development of the sign within the meaning of the speech and the appearance of new words. At the age of 19 to 31 months - a different picture. Now with the defeat of the left temporal lobe appear more gross violations of vocabulary and grammar. In this case one would expect, and a violation of the understanding of speech, it would be consistent with patterns observed in adults, but it is virtually non-existent, as the understanding of the structure by means of the right hemisphere.

As for the conventional wisdom that people with better-developed left brain different rationality, and with the right - creativity, innovation, it is again very simple straightforward solution. A study of gifted pupils, winners of Mathematical high level of competition showed that there were also distinct right-handers and left-handers, and ambidexters (people with the same sleight of hand), that is, the students had several different distribution functions hemispheres. It is known that the majority of right-handed adults (not all!) Is dominated by speech and verbal thinking left brain, left-handed and ambidexterity these functions are distributed in both hemispheres, and there is a great variation in this distribution. These children have already achieved success and, hopefully, will achieve even greater. These solutions have been and will and creativity, and rationality. Interaction hemispheres - this is a general rule for all higher mental functions.

The brain works like a computer

It is not true. Very often people's ideas about the brain and consciousness associated with technical innovation, which is at the moment. When the latest advances in technology were the hours, the brain is presented as a set of gears. Then, when there was a telephone system, the brain is often represented as a switching device that connects bundles of wires. Therefore it is not surprising that the brain began to compare with the computer, because it is the computer has become a universal tool for calculations, will allow to solve many problems that require the person of remarkable intelligence.

In fact, if we look at the way modern computers are designed and constructed as the brain, we can see that the differences between them are fundamental. The computer program stored in the memory is executed using the processor, thus, memory, and computations are separated. In the brain, as this division is not actually memory and computation it aligned with each other due to the fact that memory is stored in the structure of connections between nerve cells, which perform calculations. Therefore, the computer can easily download new software and having a processor to receive a completely different functionality. In the brain, it's almost impossible to do, because this would have to change at the same time the link between the millions of neurons.

Another important difference is that the brain has a parallel architecture, all neurons can process information independently of each other, while in most modern computers compute sequentially arranged. This allows the brain very effectively perform important tasks for the organism. The architecture of modern computers unstable errors: usually, if we remove some part of the program, it will cause failure of the entire program. The brain is able to maintain its functionality when individual cells stop working. The destruction of even fairly large areas of the brain in most cases, not much impact on the performance of their core functions. This is due to the fact that the evolution of the brain was established in order to ensure survival of the organism in the unreliability of individual cells of the nervous system.

The study of signaling substances and membrane proteins - a key part of understanding how the body works

Biophysicist talks about membrane proteins, the difficulties of their crystallization and role in the treatment of severe diseases. We spoke with the head of the Laboratory of Advanced Research membrane proteins MIPT Professor Georg Byuldt.

Before receiving a PhD, I was engaged only in physics, but after moved to biology, in a very good institute in Basel (Switzerland), Center of Biological Research, University of Basel. When you come from physics in a completely new field - biology, you have difficulty with the understanding of colleagues, all what you do, is new to you. I started with the study of lipid membranes, which then was not known structure. After some time I realized that this is the direction I is not that interesting, and just then I met a man who later became a friend of mine who told me of membrane proteins.

The role of membrane proteins in the human body

When scientists discovered cells, at the same time we found that they are surrounded by a kind of wall, which, as it turned out later, is made up of lipids and proteins. The importance of the study of proteins in the membrane wall, became apparent immediately. Within 70 years, scientists isolated one after another and examined these proteins.

Intercellular communication, as well as transmission of information within the body as a whole, made small molecules, such as hormones. These hormones bind with proteins is in the membrane, or they can not influence the behavior of the cell. Immediately it became clear that to know the structure and function of these proteins is very useful, since it is directly related to health in general to understand the processes occurring in our body. Special organs, such as brain secrete hormones that interact with cells sent, in turn, signals to the brain. That is, this system works in both directions. Therefore, the study of signaling substances and membrane proteins is a key part of understanding the body work.

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The first membrane protein that I was interested in was bacteriorhodopsin archaea. At that time, the study of its structure lasted for over 40 years. Then in Basel was coined by the method by which it became easier to crystallize membrane proteins. The first protein, crystallized in a conventional manner, the reaction became a center of photosynthetic bacteria. It crystallized Hartmut Michel, won a Nobel Prize. New same method invented by Jürg Rosenbusch, differed from him. Earlier, the proteins dissolved in Unlike membrane detergent. Rosenbusch also came up with the crystallization method directly in the membrane. Over time, this method has been very successful. For example, a conjugated structure with G-protein coupled receptor (GPCR) was identified from MIPT Vadim Cherezovs this method.

Membrane proteins, among other things, I am interested also because physics is to engage the structure definition, as in these studies it can apply the methods of physics. By studying membrane proteins, I realized that they carry out a very interesting feature, so also became engaged in spectroscopy. Then I found out that these proteins play a very important role in the communication and transfer of materials that led me to the study of membrane proteins in the context of the entire cell. Most recently, I decided to find out how to transfer signals in the cell and how proteins are transported, for example, into the mitochondrial matrix.

On difficulties with the protein crystallization

Studies at MIPT, we began to study the structure and function of membrane proteins. The main direction of the laboratory - it is the crystallization of proteins. But we also have the equipment to determine the structure, and we want to see how these proteins work inside cells. For this purpose it was acquired microscope Zeiss worth ˆ 2 million. Usually, microscopic thought of as a compact, handy tool, but it is filled with a variety of microscope devices. This is a truly beautiful machine that can use all the currently available methods for studying cells and other biological problems to solve. In the future, we will use a FT-IR spectroscopy, Raman spectroscopy, cell sorting.

In this laboratory work with solutions. For example, to create a crystal substance, it is necessary to do many operations. It is necessary to isolate the desired gene from the genome, synthesized protein, for example, a cell of a bacterium or yeast, or insect. Cells typically start with E. coli (Escherichia coli) because they are mostly used for the synthesis of proteins. When the pure material, you can proceed to crystallization. Or rather, attempts to obtain a crystal.

The difficulties here are as follows. Modern technologies allow to work with volumes measured in femtolitrah (10-15 l). We have boards with 96 cells, each of which corresponds to one attempt. Then we fill them automatically and get an image that can be viewed on a computer, and we can see, to get the desired result or not. Sometimes you have to use a hundred of these plates, that is to take 10,000 attempts to obtain a crystal, but still not get the result. Thus many attempts necessary because many of the parameters may vary: it is possible to use various surfactants, various buffer solutions, various temperatures - all this leads to a great variety of results. To achieve the desired result, all laboratories in the world have resorted to automate production of proteins crystals.

With the new method of crystallization in the membrane, this process has become a little more complicated. For membrane protein crystallization process is also automated, which was not there before, but it is more complicated than for soluble proteins.

On optogenetics and treating blindness

We've got the results for various retinal-containing proteins, which have been working on for a long time. They have become important in the context of optogenetics. Here one might ask: Why are so many to engage in retinal-containing proteins now? After all, they were important before, as they first tried to crystallize. But now the crystals have been obtained, we know their functions. So why continue to work with them? This is due to the discovery of the possibility of using the retinal-containing proteins to create and manage nerve impulses.
For example, there is a channel protein rhodopsin-2 (Channelrhodopsin-2, chr2), which serves as a channel for the passage of cations through the membrane, but this requires a signal in the form of blue light. In this case, the conformation of the protein is changed, the channel opens and cations can pass through. If you put this system in the nerve cell, it is possible to create a nerve impulse is just a flash of light. there is another protein to interrupt this momentum - galorodopsin (Halorhodopsin), which also belongs to the retinal-containing and is responsible for the transport of chloride ions. The positive charges, which were originally in the cell, you can now compensate for the negative and thus stop the momentum.

Thus, we have the perfect way to create and stopping the nerve impulse. This is one of the ways to use these proteins in optogenetics, research which is now supported by many governments. There have been many predictions that it will for the Nobel Prize this year.
The term in this direction can be obtained by a variety of useful results. Personally, I dream about the treatment of blindness, that is, the destruction of the retina. Are located behind the retina ganglion cell, that can be placed in, for example, these two proteins. Then the nerve impulses that go to the brain appear to be under the influence of light. Perhaps one day these people will have at least a black and white vision.
Another direction - is Parkinson's disease. Now it is trying to heal by introducing electrodes into certain areas of the brain and pulse action through them. Group dedicated to this, there are the Research center of Yulyuh. With the help of light, perhaps it will be possible to do much more efficiently and accurately, because the light can be controlled in a small volume, while the electric pulse applied to a significant portion of the brain.

The world today is developing a number of projects related to optogenetics, so we are also working on this. Also we are looking for other retinal-containing proteins, the structure of which we already know and that can be used in a similar way.

About the study of aging and the prospects for commercialization

Group of Vadim Cherezova trying to crystallize the novel proteins. I mentioned above involved in communication GPCR proteins. They form a plurality of more than 800 receptors, which can be divided into families extent. We would like to know the protein structure of each family, as we hope to be able to get the structures of other proteins with the help of simulation. This requires a lot of time, but it is very important because it is associated with the development of new treatments.

In our group we investigate the proteins that serve as channels for the transfer of substances through the membrane. We are also interested in Valentin Gordeliy on aging. We want to study cell death, aging, and clarify the role of membrane proteins, as well as the entire membrane aging.

In today's world, people usually die from problems such as cancer and heart attacks. But if you do not die from it, then that would be the cause of death? Suppose we cured cancer and heart attacks. What then? Scientists have different ideas on this subject. For example, when you eat, you produce free radicals that can damage DNA. Is this the ultimate cause of death or not? Around the world on these issues, many researchers are working. And since it is related to cell communication, it overlaps with the study of cell membranes.

Commercialization possible for each membrane protein - for participating in the transmission of signals, and those responsible for the transfer of substances, as they are all associated with cell health. For medical purposes it is very important to be able to create substances that interact with these proteins. Moreover, pharmaceutical companies need to improve these agents before medical use. There are great laboratories engaged in obtaining more effective drugs based on existing methods by means of computer. We could do the same. But we have to work with these companies, because when you have a good medicine, but you are running a small institution, it is not enough money to bring it to patients. You must go through many stages of costly clinical trials. Therefore, small institutions such as our work on common problems, and if we find the good stuff, or structure, then sell it a large company or make public, without receiving any money for it. Then the pharmaceutical companies will be able to start production of medicines.

We'll get the protein structure, and they will work with it further developments to pass large pharmaceutical companies, since it is usually in such small companies still do not have enough money to conduct costly tests.

The algorithm of the brain

About reflexes, the role of the emotional evaluation of the situation and the principle of the accumulation of knowledge.Is it true to understand intelligence as a set of reflexes? How does the algorithm of the brain? How do we make decisions?

It is difficult to assume that the brain consists of a set of reactions of iron, ie reflexes. However, when people ask, "Do you think that intelligence - a set of reflexes?", They all say, "Yes." This is not true. Imagine what would have behaved man whose head would be solid reflexes. He would mechanically respond to all calls: see food - rushed and ate it, he heard the call - so he started corresponding reactions, and so on. However, it is not. Furthermore, a reflex behavior is typical for machines and for slaves. The ancient Romans would execute commands such unconditional. That is, the whistle sounded - stood up, started to work. Two whistle - finished. The position is unnatural servant.

The role of qualitative assessments in the body carries the apparatus of emotions. This is a special system that provides high-quality evaluation information sets together with the motivation and behavior of all defines the general body. That is, it is necessary to choose such a result, which will give a better emotional evaluation. I assure you that not a single person and not make a step without having to not expect the end to improve his emotional evaluation. Even if he jumps off a bridge, it means only one thing: all the other actions it considers the worst for themselves. Therefore, in each situation, the body solves the optimization problem by choosing an action that should lead to a better result in terms of the emotional component. This is an optimization algorithm.

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Mathematicians speak of target functions: it must be some objective function, to aspire to the algorithm. We are talking about the two target functions. The accumulation of knowledge - it is one objective function, it is the epistemological part of the algorithm. On the other hand, it is the survival of the organism, we need to survive every minute. This optimization of the algorithm. Brain algorithm is a combination of two important algorithms: epistemological algorithm designed to search for knowledge, and optimization algorithm, which should make the best decisions on a set of already existing knowledge. On the whole brain as the control system is a self-learning (ie adaptive), recognizing, managing complex, large role in which plays the apparatus of emotions, which is the backbone subsystem organizes the entire brain. Because it is on the search for positive emotions and sent all that we do.

Molecular action of psychotropic drugs

Neuroscientist talks about the dopamine system, psychostimulants and manic psychosis. How to study the properties of dopamine produced a revolution in modern psychopharmacology? What is the effect on the dopamine system have psychostimulants? What signaling pathway causes manic psychosis?

The subjects, which for me is the main - is an attempt to understand the molecular mechanisms of action of various psychotropic drugs, ie, drugs that act on the brain. The most important discovery of modern psychopharmacology was the realization that dopamine is a neurotransmitter. Dopamine - a neurotransmitter in the brain. If you look at the scheme for the synthesis of dopamine - dopamine is formed of a well-known neurotransmitter norepinephrine. That is dopamine - a precursor of norepinephrine.

So scientists believed until 1958, while Arvid Carlsson, a great Swedish scientist, has not shown that dopamine is not just a precursor of norepinephrine, but he has a clear role in the brain. They, as well as other remarkable scientist Oleg Hornikevichem somewhere was in 1957-1958 shows that there is a brain structure that is very rich in dopamine - the so-called the striatum, which is responsible for the movement of traffic control. Oleg Hornikevich, in particular, for the first time showed that in patients with Parkinson's (as you know, parkinsonism - a movement loss, loss of control of movement) occurs devastation of dopamine in this area, in what is called the striatum.

Arvid Carlsson won the Nobel Prize for his discovery of dopamine in 2000. Unfortunately, Oleg Hornikevich similar not got - it should have received, for he was still the second discovery. They Carlsson worked as friends and competitors, have worked so closely that Arvid Carlsson discovered this animal, and Oleg Hornikevich found in humans - the effect of levodope. Levodope is a precursor of dopamine. If you give levodope or patient or experimental animal model, the movement is restored, there is dopamine. This is perhaps the most vivid manifestation of all friendly and effective impact on the neurotransmitter system that cures the disease. Since 1958 and until now levodope remains the most effective treatment for Parkinson's. Since 1958, nothing better because no one came up. In levodope has its side effects, but nevertheless it is a fact.

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The dopamine system has been very rich for pharmacology. Here are two examples of additional. In particular, Arvid Carlsson and other researchers have shown that dopamine system involved in psychosis. If you give stimulants such as amphetamine or cocaine, you're blocking dopamine reuptake mechanism. Each neuron has a way of controlling the extracellular concentrations of dopamine, ie presynaptic dopamine neuron.

If you block this protein, called the dopamine transporter, which sucks the neurotransmitter back into the neuron - that is a neurotransmitter is released, activates the receptors, and then quickly taken back into the neuron - if you block the reuptake mechanism using substances such as cocaine, amphetamine (you can transfer indefinitely: methamphetamine, ecstasy, a huge variety of psychotropic amphetamines), then you are going synaptic accumulation of neurotransmitters is over-activation postsynaptic receptors. Such psychotic reaction - you can call it euphoria. In very high doses, often psychotic reaction.

Dopamine is flashed is not only because these stimulants induce psychotic reaction, but also because the drugs have been found - so-called antipsychotics. It began with chlorpromazine, now its a huge amount: olanzapine, risperidone, can transfer indefinitely - a large number of psychotropic drugs. But all that exist today in the clinic, blocking a specific subtype of dopamine receptors. So called D2-dopamine receptor subtype. Antiparkinson agent, psychostimulants work via the dopamine system, antipsychotics work through the dopamine system.

Dopamine system was jerk, by analogy with it drugs for the serotonin system have been developed.
There-blockers such as conveyors - in the most frequent depression drugs are selective serotonin reuptake inhibitors. As noradrenaline reuptake inhibitors are used for depression. All these monoamine neurotransmitters are organized about the same.

Antidepressants are less affect the dopamine system, to a greater extent - on norepinephrine and serotonin systems. With this disease, bipolar disorder, the situation is somewhat more complicated. Experimentally it was found unexpected effects of the so-called anticonvulsants or mood stabilizers: lithium, valproate, carbamazepine.
Experimentally it was groped medicinal approaches when it is necessary to stop both manic symptoms and depression, trim, so that people do not take off in different directions. Recently, we and many other laboratories are trying to understand what is the mechanism of action of these compounds. Since monoamine drugs more or less clear. And with anticonvulsants and mood stabilizers (mood stabilizers) questions on the mechanisms of action of many.

In particular, we hit upon the mechanisms - we assume that this is not the receptor and postreceptor intraneuronal signaling pathways such as Akt / GSK3, which seem to be involved, but it is very specific stages. What's the problem with mood stabilizers, with mood stabilizers? The fact is that they do not affect monoamine receptors and transporters not affect - reuptake mechanisms.
Obviously, these substances affect the mechanisms involving monoamine transmission - psychosis and depression - it is in most cases associated with dopamine, serotonin systems. So what is the mechanism? Attempts to focus exactly on postreceptor mechanisms for intracellular signal transduction mechanisms. Here, for each receptor has a specific signaling pathway, and not one, but several. Each receptor causes signal spectrum processes. And now trying to figure out which of these signaling pathways responsible for a drug is the effect of these substances.

What was our approach? We had a mouse with enhanced dopamine transmission such giperdofaminergicheskie mouse. In these mice, we evaluated various changes in signaling pathways that are associated with enhanced dopamine transmission. And felt one way, the so-called Akt / GSK3, which was very much changed. Before us is the little attention paid. Why are we fascinated by this signaling pathway? It has been shown that, for example, lithium salts used in bipolar disorders can affect the path. But no one before us had not proved that this path is associated with dopamine receptors. And it so happened that we tied up and the effect of the monoamines antimanic agents. Several other groups have also shown it to people and animals, it seems, this is the convergence of these substances, their influence is on this path, which is associated with psychosis. That is, we try to find the signal path, which causes manic psychosis

It looks like we're getting to it. We went on to two levels of the receptor, and can go into three, four, five. Signal path - this stage, it involves a whole series of processes - the signal transfer from one molecule to another, third, fourth, and finally, to the altered function. Where can we find there something new? The problem is that if you block a receptor - and it is now quite a lot of talk in pharmacology, - you are blocking a large enough variety of signaling pathways. And you can block and affect the ways that can cause side effects. And if you work already postreceptor mechanism, you can choose the path that is associated with the disease, but will not result in any side effects.

In particular, Robert Lefkowitz proposed a theory called functional selectivity.

It is based on the fact that the receptor can cause variety of signaling processes, and for a long time it was thought that the G protein-coupled receptors mediate its signal through G-proteins. From this came the name. But the past 12 years, Bob Lefkowitz quite active on G protein-independent mechanisms, ie mechanisms, not related to G-proteins, the so-called arrestin-mediated mechanisms. This is a completely alternative signaling not associated with G-proteins. Now there is a fairly serious attempt a large number of laboratories understand the physiological and pharmacological importance of this arrestinovogo signaling pathway. Based on this developing a drug which affects either the G-protein signaling component, or a component arrestinovy. This concept is called functional selectivity, which becomes a huge scope in recent years.

Norepinephrine (Noradrenalinum)

Physiologist says about the inventing of Adrenaline, noradrenaline and pharmacological studies of its effects on behavior.

Norepinephrine and epinephrine are easily confused: similar names and chemical formulas, both of them are associated with stress and excitement, both open in the adrenal glands. However adrenaline is a hormone, norepinephrine its mainly functions as a mediator of the nervous system.
"Hormone" means that the substance is released into the blood special cells are often assembled in iron. Hormones are distributed throughout the body, acting on many organs and tissues, and their effects last for a long time - minutes and hours. Mediators released from the process of neuron (axon), forming contact with the target cell - muscular, glandular, another neuron. The mediator acts pointwise only on the cell, altering its activity is not more than a few seconds.

Adrenaline was isolated at the end of the XIX century, and immediately began to actively explore and use in clinical practice. Later, it was discovered norepinephrine. The classic work on their study carried out under the leadership of Englishman Henry Dale - one of the founders of modern pharmacology. In 1936, Dale received the Nobel Prize for the discovery and description of the mechanisms of chemical transmission of signals in the nervous system.

Conversion and Action of Noradrenaline

As adrenaline and noradrenaline in the body formed from tyrosine. Tyrosine - one of the 20 amino acids comprising the protein foods. Every day with the different foods we consume several grams of tyrosine, able to turn into norepinephrine, and then in the adrenal glands in the adrenaline. Foods rich in tyrosine, and derivatives thereof, the nervous system and activates many organs. In this regard, for example, acute cheese varieties have not advisable at night (or, say, antidepressants).
Contact axon of a neuron cell to the next, which operate neurotransmitters including noradrenaline, called a synapse. The operation of the synapse occurs when the axon comes to an electrical impulse that signals the importance of sensory stimulus, such as pain, emotions, decisions taken by the brain. Mark the end of the axon, the mediator acts on receptors - sensitive proteins located on the surface of target cells. In the case of noradrenaline receptors are classified into two types: alpha and beta, which differ in operation speed and sometimes the sign of the effect (excitation or inhibition of the following cell).

Noradrenalinum is a major mediator of the sympathetic nervous system - the part of the brain and nerve fibers that control our internal organs during stress, physical and emotional stress, energy costs. Standing out in sympathetic synapses, norepinephrine strengthens the heart, reduces the majority of the vessels. It also dilates the bronchi (so we better breathe), inhibits gastrointestinal tract (not the time to spend resources on digestion) and so on.

It is easy to guess that the first two effects are excitatory (activation of the work of the heart muscle and vascular wall cells); the other two - the brake (relaxation of bronchial walls, stomach, intestines, cessation of secretion of digestive juices). To run such divergent changes and require different types of receptors for norepinephrine - adrenoceptors. These receptors, by the way, as effectively "respond" to the emergence of adrenaline.

Noradrenalinum and stress

One of the most important effects of the sympathetic nervous system - the activation of the inner region of the adrenal glands, their "brain matter." Eye-catching due to adrenaline (with a small amount of norepinephrine) functions as a hormone. It is important that the surface of target cells adrenoceptors are present not only in the synapse zone, but also in all other areas. As a result, the adrenaline is often a significant factor in altering the activity of a variety of organs and tissues, even than norepinephrine. Epinephrine is also able to act on these types of cells, which generally are not suitable sympathetic axons: the red blood cells, liver cells, adipose tissue, and so forth.

The effects of the activation of the adrenal medulla are not only powerful, but also lasting influence of the sympathetic nervous system. As a result, serious stress necessarily involves adrenaline component. Excessive chronic stress creates constant high concentration of adrenaline in the blood. This is wrong and can lead not only to the depletion of the body, but also impairs the health disorders of the heart, stomach, intestines.

Normally very quickly arise, but the effects are short sympathetic norepinephrine harmoniously complemented stretched endocrine action of epinephrine in time. As a result, we have a complete response in the body that occurs during stress, stress, emotions and leads him into a state of readiness of the system to the optimal response.

In the brain, neurons producing neurotransmitter as norepinephrine (noradrenergic) disposed in the locus coeruleus - a small area in the upper part of the front axle. The blue spot only a few millions of nerve cells, but their axons form a very wide network of branches. As a result of the respective synapses are found in various parts of the central nervous system (CNS) - to the end of the spinal cord, including the cerebellum and cortex in the cerebral hemispheres (and present both alpha and beta adrenergic receptors in the CNS).

Functions of noradrenaline

In the most general form of norepinephrine in the CNS function can be defined as maintenance of mental stress. At the same time it affects the overall level of brain activity, our mobility and sensory perception, emotions, needs, and memory. Let's say a few words about each of the groups of effects.
Norepinephrine is involved in establishing a certain level of waking CNS activation (due primarily braking sleep centers). As a result of the higher level of stress, so we actively. Besides, everyone knows that in the context of strong emotional feelings and thoughts, we sleep less, up to insomnia. Next norepinephrine is involved in the regulation of the brake sensory streams, which allows us to focus on those signals, which are the most important here and now. It is well known analgesic effects of norepinephrine, evident in extreme situations (stress-induced analgesia). It is known that, in a state of passion, people can not notice even serious injury or physical damage.

Furthermore, norepinephrine contributes to the control of the general level of human motor activity. The synapses generated neurons of locus coeruleus, increase mobility, step speed and jogging, cutting inhibitory neurons in the motor centers. It is this component of the action of norepinephrine leads to the fact that when strong emotions and stress, we "can not sit still."

Norepinephrine is involved in learning and memorization of information occurring in the upper (cortical) areas of the central nervous system. In this case, the activity of locus coeruleus influences centers regulated positive and negative reinforcement of the brain. Isolation of norepinephrine leads to long-term changes in synaptic properties of neural networks in the cortex and cerebellum. As a result, we firmly remember the program that led to success ( "positive reinforcement"). In parallel, the brain blocks the failed program, implementation of which led to the emergence of negative emotions ( "negative reinforcement"). Against the background of high activity of locus coeruleus people and animals learn, first of all, to avoid the trouble and remember the way out of a potentially or actually dangerous situations. Against the backdrop of a small controlled stress we learn better. However, too much stress degrades the quality of memory, and if, say, a student or a student is too afraid of the exam, it is not going to benefit the cause.

Norepinephrine is important for regulating the activity of the centers of many biological needs and motivations. These centers are located in areas of the brain, the hypothalamus and the amygdala. Influencing them, norepinephrine can cause a decrease in the level of anxiety and increased aggression manifestations. The man with the high activity of locus coeruleus often has a more pronounced choleric temperament. In dangerous situations, a pair of "Fight or flee," he often chooses the second option. His brain is often more impulsive in decision-making processes, including more prone to sudden outbursts and even inappropriate aggression.
Finally, noradrenaline strongly influences the intensity of the emotional components of behavior. This refers first of all the positive emotions that arise in an apparently stressful conditions and related concepts such as the excitement, the pleasure of risk, the joy of victory. Depending on the individual organization of the brain the significance of emotions for a specific person may be different, but sometimes very large.

Balance of Noradrenaline

Sporting events (especially extreme sports), rafting on the wild rivers and climbing, casino, roller coaster, computer games - this is not an exhaustive list of ways that mankind has come up with to enhance the release of norepinephrine and obtaining related positive emotions. Here, of course, important that the adventure has ended successfully, the match was won, and the next level of "shooter" is passed. We understand that the victim computer is virtual monster. But the adrenaline that stood out in the game, is quite real, and the person might want to get it over and over again, having thrown all the other things. So there are gambling, treatment of which in severe cases require the use of the same techniques as the treatment of this drug addiction.
In general we can say that, not only participating in the carrying out of the main flow of nerve signals can seriously norepinephrine modulate, redirect these streams, and ultimately regulate the general condition of the CNS. Knowing this, it is easy enough to imagine consequences of excessive and insufficient activity of the noradrenergic system. In the first case we may encounter with hyperactivity, aggressive and psychotic symptoms, the second - with apathy, depression (due to the shortage of positive emotions), memory impairment. In the first case, as may be necessary medication with antipsychotic properties, in the second - anti-depressants. Both of these groups of drugs can influence the activity of locus coeruleus. However, the situation is complicated by the fact that the level of emotion regulation, besides noradrenaline and other mediators are involved, especially dopamine, serotonin and endorphins.

The vast majority are used in clinical practice adrenoceptor agonists and antagonists are synthetic drugs. They are the result of work with the chemically-modified molecules of adrenaline and noradrenaline. There are, however, also natural compounds that affect the system. One example - ephedrine alkaloid gymnosperms small shrub of ephedra. Ephedrine acts as a mixed agonist of the alpha and beta-adrenergic receptors. It is able to increase blood pressure, expand the bronchi, runny nose weaken, therefore the Ephedra is widely used in folk medicine. In the case of ephedrine overdose manifest its central effects: nervous agitation, altered state of consciousness. That's why ephedrine is being considered as a narcotic drug, and ephedra - as one of the plants legally prohibited for cultivation or harvesting.

After finishing the transmission of the signal, norepinephrine slightly degraded in the extracellular environment and basically sucked back to the end of the axon (presynaptic terminals). Noradrenaline reuptake proteins is carried out by special pumps. Once in the presynaptic terminals, norepinephrine may be re-released, re-transmitting the signal. But it may decompose via the enzyme monoamine oxidase (MAO). Importantly, MAO and performs the above-mentioned decomposition of dopamine and serotonin. Accordingly, drugs - blockers are potent MAO antidepressants (on the background of which is better not to have sharp cheese).

Modern methods of research and medicine

Pharmacology, starting with Henry Dale, looking for molecular "master key" to the receptor proteins. These are substances similar to noradrenaline and adrenaline (agonists) or, conversely, preventing adrenaline and noradrenaline affect the target cell (receptor antagonists). Directing their effects on the heart, blood vessels, bronchi, blood pressure can be controlled (tablets) deal with allergic asthma (inhalers), treat rhinitis ( "pinch" the capillaries of the nasal cavity using special drops) and so on. Especially important to use norepinephrine receptor antagonists in the case of hypertension. Many millions of older people around the world every day are taking such drugs to protect them from heart attacks, strokes, severely prolong life and improve its quality.

Until the last couple of decades of research into the mechanisms of synaptic norepinephrine activity is mainly conducted in experimental animals. With the advent of functional magnetic resonance imaging (fMRI) has become possible to see directly how the system works in humans with various activities and emotions. It is possible to investigate the role of the locus coeruleus and synapses in different parts of our brain. Volunteer-test is placed in a scanner, and he is given different tasks, tests. For example, he says, "Imagine that behind you chasing vicious dog", "Imagine that you are lying", "Imagine that next to you someone is very sick," or show emotionally charged videos and other modern methods (primarily. fMRI) allow visualization of CNS reactions in humans compare different temperament, age and so on.

Open questions

Department of Human and Animal Physiology of Moscow State University is actively exploring the sympathetic nervous system. In the human body many finely organized functions. One of the most difficult associated with the management of thousands of kilometers of blood vessels. The vessels in our various organs: the heart, the skin, intestine, muscle, brain - changing its diameter, and the tone is very different. During the active work on them acts as a norepinephrine and epinephrine, and severe stress their right balance is extremely important.
We know very little about the phylogeny - evolution and biodiversity effects of norepinephrine. Modern science, in addition to the human, is studying a very small number of model species: laboratory rats and mice, fruit flies, snail. And many hundreds of thousands and millions of other creatures living on the Earth, is almost unexplored. But it is known that bumble bee, octopus, gopher feel the world move, trained by similar brain working modules (although the very structure of the nervous system have very different). phylogeny studies allow, inter alia, to realize that we live in a world saturated with the most complex manifestations of life, and the person - not the only important and interesting thing on this planet.