What does the neurotransmitter gaba do: Physiology, GABA – StatPearls – NCBI Bookshelf

30.01.197016.07.2021 by alexxlab

Содержание

Physiology, GABA – StatPearls – NCBI Bookshelf

Introduction

Gamma-aminobutyric acid (GABA) is an amino acid that serves as the primary inhibitory neurotransmitter in the brain and a major inhibitory neurotransmitter in the spinal cord. It exerts its primary function in the synapse between neurons by binding to post-synaptic GABA receptors which modulate ion channels, hyperpolarizing the cell and inhibiting the transmission of an action potential. The clinical significance of GABA cannot be underestimated. Disorder in GABA signaling is implicated in a multitude of neurologic and psychiatric conditions. Modulation of GABA signaling is the basis of many pharmacologic treatments in neurology, psychiatry, and anesthesia.[1][2][3]

Cellular

GABA is synthesized in the cytoplasm of the presynaptic neuron from the precursor glutamate by the enzyme glutamate decarboxylase, an enzyme which uses vitamin B6 (pyridoxine) as a cofactor. After synthesis, it is loaded into synaptic vesicles by the vesicular inhibitory amino acid transporter. SNARE complexes help dock the vesicles into the plasma membrane of the cell. When an action potential reaches the presynaptic cell, voltage-gated calcium channels open and calcium binds to synaptobrevin, which results in the fusion of the vesicle with the plasma membrane and releases GABA into the synaptic cleft where it can bind with GABA receptors. GABA can then be degraded extracellularly or taken back up into glia or the presynaptic cell. It is degraded by GABA-transaminase into succinate semialdehyde which then enters the citric acid cycle.

GABA binds to two major post-synaptic receptors, the GABA-A and GABA-B receptors. The GABA-A receptor is an ionotropic receptor that increases chloride ion conductance into the cell in the presence of GABA. The extracellular concentration of chloride is normally much higher than the intracellular concentration. Consequently, the influx of negatively charged chloride ions hyperpolarizes the cell, inhibiting the creation of an action potential. The GABA-B receptor functions via a metabotropic G-protein coupled receptor which increases postsynaptic potassium conductance and decreases presynaptic calcium conductance, which consequently hyperpolarizes the postsynaptic cell and prevents the conduction of an action potential in the presynaptic cell. Consequently, regardless of binding to GABA-A or GABA-B receptors, GABA serves an inhibitory function.[4][5][6]

Development

Due to extracellular concentrations of chloride being lower than intracellular levels in the developing brain, GABA has an excitatory role in the fetal and neonatal brain. When GABA-A receptors open chloride channels in the developing brain, the cell becomes hypopolarized and thus more likely to fire an action potential. Consequently, drugs that increase GABA signaling have been reported to be of limited efficacy in the treatment of seizures in preterm neonates.

Organ Systems Involved

GABA is found throughout the human body, though the role that it plays in many regions remains an area of active research. GABA is the primary inhibitory neurotransmitter in the brain, and it is a major inhibitory neurotransmitter in the spinal cord. The insulin-producing beta-cells of the pancreas produce GABA. It functions to inhibit pancreatic alpha cells, stimulate beta-cell growth, and convert alpha-cells to beta cells. GABA also has been found in varying low concentrations within other organ systems, though the significance and function of this are unclear.[7]

Function

Because GABA is the fundamental neurotransmitter for inhibiting neuronal firing, its function is determined by the neural circuit that it is inhibiting. It is involved in complex circuits throughout the central nervous system. For example, GABA is released by striatal neurons in both the direct and indirect pathways projecting to the globus pallidus, which in turn extends GABA neurons to other brain areas, inhibiting unwanted motor signals. Another example is that GABA signaling in the medulla is involved in the maintenance of respiratory rate. Increased GABA signaling reduces the respiratory rate. A third example is found in the spinal cord, where GABA serves in the inhibitory interneurons. These neurons help to integrate excitatory proprioceptive signals, allowing for the spinal cord to integrate sensory information and create smooth movements.[8][9][10]

Pathophysiology

GABA is involved in several disease states:

Pyridoxine deficiency is a rare disease in which the vitamin is not available for the synthesis of GABA. It usually presents as frequent seizures during infancy that are resistant to treatment with anticonvulsants but responds very well to vitamin supplementation.
The clinical features of hepatic encephalopathy are thought to be due to elevated ammonia levels binding to the GABA-A/GABA complex and increasing chloride ion permeability.
The symptoms of Huntington disease are partially caused by a lack of GABA in the striatal projections to the globus pallidus.
Dystonia and spasticity are believed to be related to a deficiency in GABA signaling.[11][12][13]

Clinical Significance

GABA is of great clinical significance. Medications that act on the GABA receptor are commonly used as therapeutic medications and substances of abuse, and it is unlikely that any physician, regardless of specialty, will not encounter clinical situations that involve GABA.

There are numerous uses for drugs that modulate GABA signaling. Benzodiazepines are a drug class that exerts its effects by binding to the GABA-A receptor, resulting in increased chloride ion permeability by changing the frequency with which the chloride channels open. They are used in surgical anesthesia, the treatment of epilepsy, REM-sleep disorders, alcohol withdrawal, essential tremor, and muscle spasticity. They are also common drugs of abuse. Ethanol, one of the oldest and most widely-used psychoactive substances, also exerts effects on the GABA-A receptor. Alcohol withdrawal is treated with GABA modulating drugs, such as benzodiazepines. Furthermore, ethanol and benzodiazepines exhibit cross-tolerance with one another due to their similar mechanism of action. Overdosing or taking multiple GABA modulating drugs can result in respiratory depression due to increased GABA signaling in the medulla of the brain stem.

Many other drugs modulate GABA signaling, including the following:

Barbiturates, sedative drugs which increase the duration at which the chloride channel is open when GABA binds the GABA-A receptor
Vigabatrin, an antiepileptic inhibitor of GABA transaminase
Propofol, a sedative commonly used in general anesthesia and allosteric modulator and agonist of the GABA-A receptor
Flumazenil, a benzodiazepine antagonist which binds to the GABA-A receptor and can reverse benzodiazepine intoxication and improve mental status in hepatic encephalopathy
Baclofen, a muscle relaxant and GABA-B agonist
Valproic acid, a mood stabilizer and anti-epileptic that is hypothesized to have an inhibitory effect on GABA uptake
Zolpidem, a sedative-hypnotic, exerts its effects on the GABA-A receptor
Gabapentin, commonly prescribed to treat neuropathic pain, partially exerts its effects by increasing GABA synthesis via modulation of glutamate dehydrogenase[14][15][16][17]

Continuing Education / Review Questions

References

1.: Pedrón VT, Varani AP, Bettler B, Balerio GN. GABA_B receptors modulate morphine antinociception: Pharmacological and genetic approaches. Pharmacol Biochem Behav. 2019 May;180:11-21. [PubMed: 30851293]
2.: Kondziella D. The Top 5 Neurotransmitters from a Clinical Neurologist’s Perspective. Neurochem Res. 2017 Jun;42(6):1767-1771. [PubMed: 27822666]
3.: Olsen RW. GABA_A receptor: Positive and negative allosteric modulators. Neuropharmacology. 2018 Jul 01;136(Pt A):10-22. [PMC free article: PMC6027637] [PubMed: 29407219]
4.: Südhof TC. Neurotransmitter release: the last millisecond in the life of a synaptic vesicle. Neuron. 2013 Oct 30;80(3):675-90. [PMC free article: PMC3866025] [PubMed: 24183019]
5.: Leinekugel X, Khalilov I, McLean H, Caillard O, Gaiarsa JL, Ben-Ari Y, Khazipov R. GABA is the principal fast-acting excitatory transmitter in the neonatal brain. Adv Neurol. 1999;79:189-201. [PubMed: 10514814]
6.: Allen MJ, Sabir S, Sharma S. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Jul 26, 2020. GABA Receptor. [PubMed: 30252380]
7.: Khanna A, Walcott BP, Kahle KT. Limitations of Current GABA Agonists in Neonatal Seizures: Toward GABA Modulation Via the Targeting of Neuronal Cl(-) Transport. Front Neurol. 2013;4:78. [PMC free article: PMC3691543] [PubMed: 23805124]
8.: Wang Q, Ren L, Wan Y, Prud’homme GJ. GABAergic regulation of pancreatic islet cells: Physiology and antidiabetic effects. J Cell Physiol. 2019 Jan 28; [PubMed: 30693506]
9.: Tong Y. Seizures caused by pyridoxine (vitamin B6) deficiency in adults: A case report and literature review. Intractable Rare Dis Res. 2014 May;3(2):52-6. [PMC free article: PMC4204538] [PubMed: 25343127]
10.: Raymond LA. Striatal synaptic dysfunction and altered calcium regulation in Huntington disease. Biochem Biophys Res Commun. 2017 Feb 19;483(4):1051-1062. [PubMed: 27423394]
11.: Hammond JB, Ahmad F. Hepatic encephalopathy and role of antibenzodiazepines. Am J Ther. 1998 Jan;5(1):33-6. [PubMed: 10099035]
12.: Termsarasab P, Thammongkolchai T, Frucht SJ. Medical treatment of dystonia. J Clin Mov Disord. 2016;3:19. [PMC free article: PMC5168853] [PubMed: 28031858]
13.: Yamada KA, Norman WP, Hamosh P, Gillis RA. Medullary ventral surface GABA receptors affect respiratory and cardiovascular function. Brain Res. 1982 Sep 23;248(1):71-8. [PubMed: 6289995]
14.: Ahnert-Hilger G, Kutay U, Chahoud I, Rapoport T, Wiedenmann B. Synaptobrevin is essential for secretion but not for the development of synaptic processes. Eur J Cell Biol. 1996 May;70(1):1-11. [PubMed: 8738414]
15.: Wan Y, Wang Q, Prud’homme GJ. GABAergic system in the endocrine pancreas: a new target for diabetes treatment. Diabetes Metab Syndr Obes. 2015;8:79-87. [PMC free article: PMC4322886] [PubMed: 25678807]
16.: Korpi ER, Sinkkonen ST. GABA(A) receptor subtypes as targets for neuropsychiatric drug development. Pharmacol Ther. 2006 Jan;109(1-2):12-32. [PubMed: 15996746]
17.: Jembrek MJ, Vlainic J. GABA Receptors: Pharmacological Potential and Pitfalls. Curr Pharm Des. 2015;21(34):4943-59. [PubMed: 26365137]

Physiology, GABA – StatPearls – NCBI Bookshelf

Introduction

Cellular

Development

Organ Systems Involved

Function

Pathophysiology

GABA is involved in several disease states:

Pyridoxine deficiency is a rare disease in which the vitamin is not available for the synthesis of GABA. It usually presents as frequent seizures during infancy that are resistant to treatment with anticonvulsants but responds very well to vitamin supplementation.
The clinical features of hepatic encephalopathy are thought to be due to elevated ammonia levels binding to the GABA-A/GABA complex and increasing chloride ion permeability.
The symptoms of Huntington disease are partially caused by a lack of GABA in the striatal projections to the globus pallidus.
Dystonia and spasticity are believed to be related to a deficiency in GABA signaling.[11][12][13]

Clinical Significance

Many other drugs modulate GABA signaling, including the following:

Barbiturates, sedative drugs which increase the duration at which the chloride channel is open when GABA binds the GABA-A receptor
Vigabatrin, an antiepileptic inhibitor of GABA transaminase
Propofol, a sedative commonly used in general anesthesia and allosteric modulator and agonist of the GABA-A receptor
Flumazenil, a benzodiazepine antagonist which binds to the GABA-A receptor and can reverse benzodiazepine intoxication and improve mental status in hepatic encephalopathy
Baclofen, a muscle relaxant and GABA-B agonist
Valproic acid, a mood stabilizer and anti-epileptic that is hypothesized to have an inhibitory effect on GABA uptake
Zolpidem, a sedative-hypnotic, exerts its effects on the GABA-A receptor
Gabapentin, commonly prescribed to treat neuropathic pain, partially exerts its effects by increasing GABA synthesis via modulation of glutamate dehydrogenase[14][15][16][17]

Continuing Education / Review Questions

References

1.: Pedrón VT, Varani AP, Bettler B, Balerio GN. GABA_B receptors modulate morphine antinociception: Pharmacological and genetic approaches. Pharmacol Biochem Behav. 2019 May;180:11-21. [PubMed: 30851293]
2.: Kondziella D. The Top 5 Neurotransmitters from a Clinical Neurologist’s Perspective. Neurochem Res. 2017 Jun;42(6):1767-1771. [PubMed: 27822666]
3.: Olsen RW. GABA_A receptor: Positive and negative allosteric modulators. Neuropharmacology. 2018 Jul 01;136(Pt A):10-22. [PMC free article: PMC6027637] [PubMed: 29407219]
4.: Südhof TC. Neurotransmitter release: the last millisecond in the life of a synaptic vesicle. Neuron. 2013 Oct 30;80(3):675-90. [PMC free article: PMC3866025] [PubMed: 24183019]
5.: Leinekugel X, Khalilov I, McLean H, Caillard O, Gaiarsa JL, Ben-Ari Y, Khazipov R. GABA is the principal fast-acting excitatory transmitter in the neonatal brain. Adv Neurol. 1999;79:189-201. [PubMed: 10514814]
6.: Allen MJ, Sabir S, Sharma S. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Jul 26, 2020. GABA Receptor. [PubMed: 30252380]
7.: Khanna A, Walcott BP, Kahle KT. Limitations of Current GABA Agonists in Neonatal Seizures: Toward GABA Modulation Via the Targeting of Neuronal Cl(-) Transport. Front Neurol. 2013;4:78. [PMC free article: PMC3691543] [PubMed: 23805124]
8.: Wang Q, Ren L, Wan Y, Prud’homme GJ. GABAergic regulation of pancreatic islet cells: Physiology and antidiabetic effects. J Cell Physiol. 2019 Jan 28; [PubMed: 30693506]
9.: Tong Y. Seizures caused by pyridoxine (vitamin B6) deficiency in adults: A case report and literature review. Intractable Rare Dis Res. 2014 May;3(2):52-6. [PMC free article: PMC4204538] [PubMed: 25343127]
10.: Raymond LA. Striatal synaptic dysfunction and altered calcium regulation in Huntington disease. Biochem Biophys Res Commun. 2017 Feb 19;483(4):1051-1062. [PubMed: 27423394]
11.: Hammond JB, Ahmad F. Hepatic encephalopathy and role of antibenzodiazepines. Am J Ther. 1998 Jan;5(1):33-6. [PubMed: 10099035]
12.: Termsarasab P, Thammongkolchai T, Frucht SJ. Medical treatment of dystonia. J Clin Mov Disord. 2016;3:19. [PMC free article: PMC5168853] [PubMed: 28031858]
13.: Yamada KA, Norman WP, Hamosh P, Gillis RA. Medullary ventral surface GABA receptors affect respiratory and cardiovascular function. Brain Res. 1982 Sep 23;248(1):71-8. [PubMed: 6289995]
14.: Ahnert-Hilger G, Kutay U, Chahoud I, Rapoport T, Wiedenmann B. Synaptobrevin is essential for secretion but not for the development of synaptic processes. Eur J Cell Biol. 1996 May;70(1):1-11. [PubMed: 8738414]
15.: Wan Y, Wang Q, Prud’homme GJ. GABAergic system in the endocrine pancreas: a new target for diabetes treatment. Diabetes Metab Syndr Obes. 2015;8:79-87. [PMC free article: PMC4322886] [PubMed: 25678807]
16.: Korpi ER, Sinkkonen ST. GABA(A) receptor subtypes as targets for neuropsychiatric drug development. Pharmacol Ther. 2006 Jan;109(1-2):12-32. [PubMed: 15996746]
17.: Jembrek MJ, Vlainic J. GABA Receptors: Pharmacological Potential and Pitfalls. Curr Pharm Des. 2015;21(34):4943-59. [PubMed: 26365137]

What are the benefits of increased GABA levels in the brain?

Gamma-aminobutyric acid (GABA) is a neurotransmitter, or chemical messenger, in the brain. It blocks specific signals in the central nervous system, slowing down the brain. This provides a protective and calming effect on the brain and body.

The body produces GABA, and it may also be present in some fermented foods, such as kimchi, miso, and tempeh. These are not foods that most people include in their daily diets, so some people take GABA supplements to achieve the benefits.

In this article, we examine how increased levels of GABA may impact the brain and body, and whether taking GABA supplements could have the same benefits.

The brain contains many neurotransmitters that trigger or inhibit specific reactions in the body.

GABA is a neurotransmitter that inhibits or slows the brain’s functions. This activity produces effects such as:

relieving anxiety
reducing stress
improving sleep
preventing brain damage

The brain naturally releases GABA at the end of a day to promote sleepiness and allow a person to rest. Some of the medications doctors prescribe to induce sleep and reduce anxiety may also increase the action of GABA.

Some experts have suggested that increased levels of GABA may have benefits, but the evidence is not clear. According to a 2019 review, GABA has anti-microbial, anti-seizure, and antioxidant properties and may help treat and prevent conditions such as:

Medications to increase GABA

Doctors may prescribe medicines that increase the amount of GABA or stimulate the same neurotransmitters in the brain to treat some medical conditions, such as epilepsy.

For example, benzodiazepines (Valium, Xanax) act on many of the same neurotransmitter receptors as GABA. According to one study, people who have depression may have reduced GABA levels in the brain. The use of benzodiazepines may be beneficial in those instances.

Doctors also prescribe the medication gabapentin (Neurontin), which is chemically similar to GABA to reduce seizures and muscle pain.

However, doctors are not clear whether the therapeutic effects of these medications are related to their effect on GABA receptors or whether they work in other ways.

Some people take supplements of GABA for their supposed stress- and anxiety-relieving benefits.

The Food and Drug Administration (FDA) has approved GABA for use as a supplement and as a food additive. Manufacturers may add GABA to:

sports drinks
snack bars
chewing gum
candies, and more

Manufacturers produce GABA supplements by fermenting a form of lactic acid bacteria.

However, the FDA do not regulate dietary supplements in the same way as medications. Therefore, consumers should exercise caution as to where they purchase the product from and only buy from reputable vendors and companies.

Some people may take a supplement in pill form, while others may add it to foods, such as protein drinks.

Researchers have not established a daily recommended intake or a suggested upper limit for GABA. Anyone wanting to take GABA as a supplement should consider talking to their doctor first.

At present, there is not enough research to evaluate the possible side effects of taking GABA supplements. However, if a person does experience side effects that might be GABA-related, they should discontinue the use of the supplement and contact their doctor.

Some researchers have voiced concerns about the supposed positive benefits of taking GABA supplements. An article in the journal Frontiers in Psychology notes that experts remain unclear whether GABA offers real benefits or whether the effects that people report experiencing are a placebo response.

Other researchers do not believe that GABA supplements cross the blood-brain barrier, which they would have to do to have any effect on the body.

However, some studies report positive effects from taking GABA supplements. These include:

Enhanced thinking and task performance abilities

A study from 2015 found that taking 800 milligrams (mg) of GABA supplementation per day enhanced a person’s ability to prioritize and plan actions. Although the study was small, involving just 30 healthy volunteers, it showed how GABA supplementation might promote enhanced thinking.

Stress reduction

An older study from 2012 found that taking 100 mg of GABA daily helped reduce stress due to mental tasks. Like many other studies related to GABA, the study was small and involved just 63 participants.

Workout recovery and muscle building

A 2019 research study asked 21 healthy males to take a supplement with whey protein or whey protein plus GABA once a day for 12 weeks.

The participants performed the same resistance training exercises twice a week, and the researchers measured the results. The researchers found that the combination of whey protein and GABA increased levels of growth hormone compared to whey protein alone.

Although this was another small study, the researchers concluded that GABA supplements might help to build muscle and assist in workout recovery. They recommended that researchers conduct more studies.

GABA naturally plays an essential role in promoting sleep, relieving anxiety, and protecting the brain.

Scientists have not been able to prove the positive effects of GABA supplementation on a large scale, and their use may have limited effectiveness.

If a person has received a diagnosis for conditions such as depression, anxiety, or attention deficit hyperactivity disorder, they may wish to talk to their doctor about medically-proven treatment before taking GABA supplements.

GABA, GABA, GABA, what does it actually do in the brain?

GABA molecular structure. Credit: Wikipedia

Gamma-Aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the brain. It is the control knob of all control knobs. But why GABA? What, if anything, might be so special about the molecule?

To look at it, there is nothing inherently peculiar about the small four-carbon backbone structure of GABA. Solvation effects in solution allow GABA to take on five different possible conformations, some compact, and others more extended. At the receptor level, this flexibility means that GABA is a highly ‘druggable’ target. In other words, pharmaceutical analogs of GABA are more rigidly pocketable in select receptor subsets, and therefore potentially very specific.

If GABA itself is completely ordinary, does it, perhaps by chance, sit in some prized location within metabolism? Some of the apex positions in metabolic cycles are occupied by molecules like Acetyl-CoA and ATP. Acetyl-CoA sits right at the intersection of glycolysis, the TCA cycle, ketone production, β-oxidation of lipids, and fatty acid elongation. It even plugs directly into synthesis of the neurotransmitter acetylcholine. Curiously, there are no major receptor systems associated with this complex molecule that might otherwise keynote its position inside the cell.

ATP has a more condensed footprint than Acetyl-CoA, but it is certainly no slouch. It directly links oxidative phosphorylation with nucleotide metabolism, and is piloted by its own special set of membrane receptors. Like the GABA ecosystem, ATP comes with the full-service suite containing all the expected ionotropic and metabotropic receptor functions. In the case of GABA, these receptor effects have traditionally been neatly grouped into GABAA receptors, which act as channels for chloride ions, and GABAB receptors, which signal through G-protein bound to their undercarriage.

This tidy picture was recently shaken up with reports of GABA directly gating potassium (K) channels. K channels respond to voltage and normally act to hyperpolarize a neuron, or repolarize a it after a spike. The authors of a paper just published in Nature found that the KCNQ receptor family has an evolutionarily conserved spot set aside just for GABA. When GABA is present there, the voltage set point of these channels is shifted to a more polarized state.

KCNQ channels carry the so-called ‘M’ current, which can be triggered by the agonist muscarine. Because of this receptor-like action, lack of inactivation, and voltage range of operation, these M channels are said to be regulators of neuronal excitability. Often, this just means they convert a neuron from a phasic to a tonic firing pattern. In some cases, neurons with strong M currents might be idealized as voltage controlled oscillators (VCOs). Such a device takes an analog voltage input and generates a variable frequency output. A variation of the VCO, pulse-code modulation, is now the general method of encoding used for uncompressed audio.

While this newfound ability of K ion channel sensitivity is undoubtedly big news in the electrophysiology world, I am going to go out a limb and suggest that the secret of GABA is probably not doing digital audio in your brain. In this void, I think we must dig deeper into what those other kinds of receptors, the slow and roundabout GABAB metabotropic receptors, might be doing. For that matter, we need to break out of the GABA bubble and ask what any G-protein coupled receptor is really doing for the cell.

One clue is that all of these receptors invariably provide for some external control of GTP nucleotide hydrolysis. In that capacity, they are also acting as ‘honest signalers’ of GTP and GDP status. Furthermore, depending on whether the G protein alpha subunit is itself excitatory or inhibitory, the next second messenger down the line (in this case, adenylate or guanylate cyclase), also deals in nucleotides. Namely, they each cleave a double phosphate from their respective namesake trinucleotide, and then lock the remaining molecule up in a knot until phosphodiesterases eventually cleave it.

Who in the cell would be interested in nucleotides? Neurons are generally stuck in the senescence G0 phase of their cell cycle and aren’t worried about having enough nucleotide for the next cell division. There is none coming. Their nuclei only need to maintain a small but steady deoxynucleotide reserve to meet the requirements of DNA repair. In humans, this amount to about 10,000 oxidative lesions per nucleus per day. Therefore, neurons are at liberty to downregulate de-novo nucleotide synthesis enzymes, as well as some of their high-end replication-linked repair pathways.

Mitochondria, on the other hand, are extremely interested in nucleotides. While they have various nucleotide salvage and repair pathways on hand, demand is high—mitochondrial DNA is constantly subjected to mutations and partial deletions, it must be continually refreshed as mitochondria replicate themselves and their nucleoids.

Is there any evidence that GABA signaling and metabolism are directly involved with nucleotide status?

The ‘GABA shunt’ is a detour on the TCA cycle that figures prominently in the nervous system. The cortex in particular is literally one big fat GABA shunt. The detailed molecular structure of the cortex is what you get when you blow up this particular region of metabolism and build an entire higher brain lobe around it. What I mean by this is that our most refined neural wetware runs a relatively simple GABA-glutamate-glutamine metabolic cycle on an elaborate tripartite synaptic hardware; it is a co-op where three different kinds of mitochondria, those optimized by interneuron, pyramidal cell, and astrocyte, exist in mutual communication with each other across a continually fluctuating membranous border.

The take-off point for the GABA shunt lies at alpha-ketoglutarate in the TCA cycle, and the re-entry point connects up at the succinate. A major branch point, succinate is another apex molecule with a hand in everything. Like acetyl-CoA, it links to all major energy pathways, and even contributes to special orders like cholesterol and heme. Similarly, succinate also comes in an acetylated version, and it sits right between succinate and alpha-KG on the TCA cycle.

GABA-glutamate-glutamine cycle at cortical synapses. Credit: studyblue.com

The key observation here is that the enzyme that converts it into succinate, succinyl-CoA ligase (aka. succinyl-CoA synthase), has one very important feature: When it is operating in the forward direction of the cycle, it also generates purine nucleotides as part of the deal. Different tissues in the body build slightly different versions of this enzyme by substituting in alternate secondary subunits. The SUCLG2 version makes GTP in anabolic tissue like the liver and kidneys, while and the SULCA2 version makes ATP for catabolic tissue like brain and muscle. When either of these subunits are mutated, you end with mitochondrial disorder. The exact symptoms depend on which variants you have, and in which tissues.

It is worth mentioning here that some of the most puzzling mental phenomena in all annals of medicine occur when there are genetic defects in the enzymes needed in nucleotide metabolism, particularly in those that localize to mitochondria. Cases in point are the bizarre symptomatology of purine-salvage pathways linked to Lesch-Nyhan syndrome, or to stiff-person syndrome, as well as several unique forms of seizure.

On the far side of succinate on the TCA is fumarate. Fumarate can also enter the cycle by way of a reserve purine cycle that kicks into gear in active tissue when metabolic demand is high. Normal operation of the TCA cycle generates fumarate from succinate via succinate dehydrogenase in the inner mitochondrial membrane. This enzyme simultaneously functions as in respiratory chain electron transport as Complex II.

The GABA shunt. Credit: frontiers.org

We can see from the diagram above that the GABA shunt appears to bypass this critical nucleotide-generating step of succinyl-CoA synthase. However, researchers have previously found that a GABA transaminase (ABAT) shunt enzyme operates in a complex with the SulcA2 subunit and may also act in the final steps of purine salvage. They also believe that a nucleoside diphosphate kinase (NME4) that posses a mitochondrial localization sequence is part of the complex, although there is still some question as to actual levels of this enzyme in the brain.

Some additional insight into what exactly might be going on was recently provided by the discovery of a new mechanism for generating GABA in the brain without the GABA shunt. Normally, only neurons make GABA from glutamate because only they have the GAD enzyme to do it. But glia can also generate GABA by degrading putrescine via monoamine oxidase B (MAOB) in the mitochondrial outer membrane. This is particularly useful in the cerebellum, where glial Bergman cells, which are responsible for generating and maintaining its highly organized architexture, are abundant. Bergmann glia form palisades aligned with the long axis of the cerebellar folium at a ratio of eight glia to one Purkinje cell, and each glia coordinates around 5000 synapses per Purkinje cell.

Cerebellar ataxias and retinal problems are two common issues that regularly arise across the spectrum of mitochondrial disorders. Since MAOB is coded on the X chromosome, males (who get their X from mom) would inherit it as a package deal together with their mtDNA. This is because we all get our mitochondria exclusively from our mothers. Looking at these kinds of co-inherited linkages is an important tool for probing mitochondrial disease. This information is also important to determine what kinds of drugs should be used in treatments.

For example, vigabatrin is a roundly horrific medicine that causes visual field defects in almost half of the kids who are treated with it. Unfortunately, this is often the only drug that works against some kinds of equally horrible seizures. The researchers mentioned above used vigabatrin experimentally to demonstrate the nucleotide synthesis pathways involved with ABAT. While it is a close structural analog of GABA, vigabatrin acts as a potent suicide inhibitor of ABAT, but it won’t bind all to GABA receptors. GABA levels, mitochondrial levels, and mtDNA levels are all been proven to be very sensitive to precise amounts of vigabatrin given. Undesirable effects of vigabatrin might be expected if given to individuals with pre-existing mitochondrial disease.

It was also recently found that a molecule called torin 1 can at least partially correct for some of the primary and incidental effects of vigabatrin. The mechanism involves the ability of GABA to activate mTOR (mechanistic target of rapamycin), which, in turn, blocks elimination of spent or superfluous mitochondria through mitophagy. This also means that more mitochondria with damaged mtDNA will persist. Torin, an inhibitor or mTor (similar to rapamycin), may therefore be a useful tool for dealing with some of the negative effects of vigabatrin in active tissue like the eye and brain.

The authors of the torin study observed some seemingly paradoxical effects in different parts of the brain. For example, they lacked a satisfying explanation for why torin 1 normalized mitochondrial accumulation in the hippocampus, but not in the eye, liver, or parietal cortex, and also why hippocampal mitochondria were increased with vigabatrin, but not in the parietal cortex.

One thing that distinguishes the nervous system from all other non-thinking organs—perhaps its single most defining feature—is its massive, and largely polarized, intracellular conduction of mitochondria. When required, this activity leads to transcellular conduction of mitochondria, often followed by mitophagy, as is well known to be important in the optic nerve.

Such transexudation circuits, perhaps locally between the hippocampus and associated cortical regions, or even more peripherally from the nervous system to other organs, would naturally compensate for metabolic shortfalls that invariably arise in single cells that lack specific enzymes as a result of their genetic differentiation. The GABA shunt is one nice example of this.

Mitochondria are not uniform and faceless like electrons. They age, albeit differentially, sometimes reversibly, and are sorted accordingly in cells and tissues. Spiking in the brain is the direct result of metabolic activity, and seizing the result when things are too far off kilter. We know spikes control mitochondria, their activities, and more visibly, their movements. Now, we also know that one way spikes achieve this control is by manipulating nucleotide metabolism in mitochondria.

The relevance of GABA for diabetes highlighted in two new studies

More information:
Rían W. Manville et al. Direct neurotransmitter activation of voltage-gated potassium channels, Nature Communications (2018). DOI: 10.1038/s41467-018-04266-w

Citation:
GABA, GABA, GABA, what does it actually do in the brain? (2018, May 16)
retrieved 16 July 2021
from https://medicalxpress.com/news/2018-05-gaba-brain.html

This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no
part may be reproduced without the written permission. The content is provided for information purposes only.

3 Amazing Benefits of GABA

Source: Deposit Photo

GABA is one of the supplements patients ask me about a lot, often with looks of confusion on their faces. I think the confusion comes from the fact that GABA is both a chemical produced within the body and a supplement that’s made for ingestion. Unlike melatonin, which is also produced within the body and as a supplement, GABA isn’t nearly as well known—nor has it received nearly the amount of scientific attention. Given the interest and popularity of GABA—and the importance of the body’s own GABA for mood, and health—it’s definitely worth spending some time talking about.

What is GABA?

Gamma-Aminobutyric acid is an amino acid produced naturally in the brain. GABA functions as a neurotransmitter, facilitating communication among brain cells. GABA’s big role in the body is to reduce the activity of neurons in the brain and central nervous system, which in turn has a broad range of effects on the body and mind, including increased relaxation, reduced stress, a more calm, balanced mood, alleviation of pain, and a boost to sleep.

Many medications interact with GABA and GABA receptors in the brain, altering their function to achieve certain effects, typically relaxation, pain relief, stress and anxiety reduction, lower blood pressure, and improved sleep. Barbiturates, anesthetics, benzodiazepines, antidepressants, and anti-seizure medications are some of the medications that target GABA.

A number of natural supplements also affect GABA activity, to help relieve stress and anxiety, promote a balanced mood, and help with sleep. I’ve written about valerian and hops, magnesium, and L-theanine, all of which have an effect on the brain’s GABA activity. Other natural supplements that may affect GABA activity include L-arginine, kava, passionflower, and American ginseng.

GABA is found naturally in varieties of green, black, and oolong tea, as well as in fermented foods including kefir, yogurt, and tempeh. Other foods contain GABA or may boost its production in the body, including whole grains, fava beans, soy, lentils, and other beans; nuts including walnuts, almonds, and sunflower seeds; fish including shrimp and halibut; citrus, tomatoes, berries, spinach, broccoli, potatoes, and cocoa.

GABA is also available as a supplement. GABA supplements are often used to treat high blood pressure, stress and anxiety, and sleep, as well as to stimulate the body’s natural growth hormone, often by athletes.

How does GABA work?

I call GABA the brakes of the brain. It is the body’s most important inhibitory neurotransmitter, which means it lowers the activity of neural cells in the brain and central nervous system, having the effect of moving the brain and the body into lower gear. By inhibiting neural activity, GABA facilitates sleep, reduces mental and physical stress, lowers anxiety, and creates a calmness of mood. GABA also plays an important role in regulating muscle tone. In combination with glutamate, the body’s most important excitatory neurotransmitter, GABA is an important contributor to the body’s overall mental and physical homeostasis, or balance.

GABA plays a role in the healthy functioning of the body’s immune and endocrine systems, as well as in the regulation of appetite and metabolism. There’s also interesting emerging research about GABA’s role in gut health and gastrointestinal function, where it may work to support motility, control inflammation and support immune system function, and help regulate hormone activity.

Low GABA activity in the body can result in:

Anxiety.
Chronic stress.
Depression.
Difficulty concentrating and memory problems.
Muscle pain and headaches.
Insomnia and other sleep problems.
Low GABA activity is also associated with substance use disorders.

There is ongoing investigation and debate about how GABA supplements work in the body, and how their mechanisms of action may differ from the body’s internally-produced GABA. Specifically, scientists have not reached consensus about whether, or how effectively, supplemental GABA crosses what’s known as the blood-brain barrier — meaning, how well it moves from the bloodstream directly into the brain. There remains real need for additional research into the effects of supplemental GABA, including how it may affect the nervous system via the gut.

Below, I’ll discuss what science tells us today about the potential effectiveness of GABA supplements for sleep and other conditions.

Benefits of GABA

For sleep: The body’s own GABA activity is important for sleep. GABA enables the body and mind to relax and fall asleep, and to sleep soundly throughout the night. Low GABA activity is linked to insomnia and disrupted sleep. In one study, GABA levels in people with insomnia were almost 30 percent lower than in people without the sleep disorder. And these low GABA levels also corresponded to more restless, wakeful sleep. Sleep medications including those with zolpidem (Ambien and others) and eszopiclone (Lunesta and others) target the body’s GABA system to increase sedation and sleep. Research indicates that one negative side effect of these sleep medications — hallucinations — may result from their alterations to GABA activity.

There’s relatively limited research on the direct benefits of supplemental GABA for sleep. Some recent research suggests that GABA produced in fermented food may increase sleep time and decrease the time it takes to fall asleep. Another recent study showed that a combination of GABA and 5-HTP may together improve sleep quality and increase sleep time. Given the importance of GABA to the body’s sleep patterns, more research into the effects of GABA supplements on sleep is sorely needed.

For stress and anxiety: As a natural chemical the body produces, GABA’s primary role is to diminish the activity of neurons in the brain and central nervous system, which puts the body in a greater state of relaxation and alleviates stress and anxiety. Supplemental GABA may benefit sleep by aiding relaxation and providing relief from anxiety and stress. There remains debate among researchers about supplemental GABA’s effectiveness in reducing anxiety and stress because of longstanding questions over supplemental GABA’s ability to enter the brain from the bloodstream. (It’s important to note that GABA, in supplement form, may have other ways of relaxing the body, including possibly through GABA’s activity in the gut microbiome.)

While the scientific debate goes on, some studies have shown GABA to be effective in lowering anxiety and boosting relaxation. One small study of 13 adults showed GABA to be effective as a relaxant and anxiety reliever, with slowed brain waves seen within an hour of taking the supplement. This study also found that a boost to the immune system also occurred with GABA, suggesting supplemental GABA may enhance immunity in people undergoing mental stress.

Another larger study investigated the effects of 100 milligrams of GABA among a group of people who’d recently undertaken a stressful mental task. Scientists measured a slowing down of brain waves in people who’d taken GABA, pointing to an alleviation of mental stress. Another study tested the effects of GABA in people who were about to take a stressful math test. Those who ate chocolate infused with GABA rebounded more quickly from test-related stress, including stress-lowering changes to heart-rate variability.

For high blood pressure: GABA supplements are sometimes used by people as a natural way to lower blood pressure. There is evidence indicating that GABA may work to reduce high blood pressure. In one study of people with borderline high blood pressure, 12 weeks of use of the supplement chlorella, a type of algae rich in GABA, significantly lowered blood pressure. In addition to being important on its own, maintaining healthy blood pressure can also help protect your sleep. A natural drop in blood pressure at night is one part of the body’s progression into sleep. High blood pressure can be a sign of hyperarousal, a state of physical alertness and vigilance that can make it difficult to fall asleep and stay asleep. Poor sleep and sleep disorders, particularly sleep apnea, contribute to high blood pressure, and can lead to the kind of hypertension that is difficult to treat.

What to know

Always consult your doctor before you begin taking a supplement or make any changes to your existing medication and supplement routine. This is not medical advice, but it is information you can use as a conversation starter with your physician.

Dosing

The following doses are based on amounts that have been investigated in scientific studies. In general, it is recommended that users begin with the lowest suggested dose, and gradually increase as needed.

For sleep, stress and anxiety: 100-200 mg and higher doses, in scientific studies. Individual dosing and length of use will vary.
For high blood pressure: 10-20 mg, in scientific studies.

Possible side effects

GABA oral supplements are generally well tolerated by healthy adults. Some people may experience negative side effects, including:

Gastric distress.
Nausea.
Diminished appetite.
Constipation.
Burning throat.
Drowsiness and fatigue.
Muscle weakness.
Shortness of breath, at very high doses.

Interactions

These are commonly used medications and supplements that have scientifically-identified interactions with GABA. People who take these or any other medications and supplements should consult with a physician before beginning to use GABA as a supplement.

Interactions with medications

High blood pressure medications. GABA can lower blood pressure. If you take GABA in addition to taking blood pressure medication, your blood pressure may drop too low.
Antidepressant medications. People taking antidepressants should consult with their physician before taking GABA.
Neurally-active medications. People taking medications that affect brain activity should consult their physician before taking GABA.

Interactions with other supplements

Herbs and supplements that may lower blood pressure. Because GABA may lower your blood pressure, if you take GABA along with other herbs or supplements that also may lower blood pressure, the combination may lead to your blood pressure dropping too low.Herbs and supplements that lower blood pressure include, but are not limited to:
- Cocoa.
- Alpha-linolenic acid.
- Blond psyllium, and other fiber supplements.
- Cod liver oil.
- Magnesium.
- Calcium.
- Potassium.
- Folic acid.
- Coenzyme Q10.
- L-arginine.
- Garlic.
- Omega-3 fatty acids.

Cocoa.
Alpha-linolenic acid.
Blond psyllium, and other fiber supplements.
Cod liver oil.
Magnesium.
Calcium.
Potassium.
Folic acid.
Coenzyme Q10.
L-arginine.
Garlic.
Omega-3 fatty acids.

I’ve seen patients experience relief from anxiety, reduced stress, and improved sleep via the relaxing impact of supplemental GABA. I don’t think we’ve seen nearly enough research to have a sufficient understanding of how GABA supplements might affect stress, mood, and sleep, or other ways GABA as a supplement may benefit emotional, cognitive, and physical health. As we learn more—which I hope we do, soon—I’ll be sure to update you.

What is GABA? – Function, Benefits & Side Effects – Video & Lesson Transcript

GABA as a Supplement

The nutrient supplement industry makes two important claims about the effects of GABA when ingested orally:

GABA reduces anxiety by suppressing the circuitry in the brain that causes the anxiety
GABA increases growth hormone secretion, thus increasing muscle mass

Let’s look at each of these claims and see if they are true, starting with suppressing anxiety.

Your body is designed to take good care of your central nervous system (CNS), which consists of your brain and spinal cord. The main mechanism is the blood brain barrier. Your CNS is surrounded by a tough membrane that contains very small blood vessels called capillaries. In many areas of the body, capillaries exchange substances contained in the blood with surrounding tissues, such as oxygen and glucose. The same occurs in the brain but is highly regulated. These particular capillaries are surrounded by cells that are packed tightly together.

Therefore, only certain substances can pass through, thus creating a barrier of sorts that helps to protect the CNS. When it comes to GABA, it is already produced within the brain and used as a neurotransmitter. If you were to ingest a GABA supplement, it would have to pass through the blood brain barrier to reach the brain. Does it? Mostly no. It does so at very low levels, which means the barrier blocks the majority of GABA from reaching the brain. Therefore, It appears that GABA supplements don’t really reduce the activity of brain circuits responsible for increased anxiety. However, more studies are necessary to know for certain.

Let’s see if it works at causing the secretion of growth hormones.

This hormone is located in the Anterior pituitary of your brain. When secreted into the bloodstream, it causes an increase in muscle tissue production. Body builders and other athletes exploit this process by consuming growth hormone supplements. However, the supplements enter the bloodstream directly and don’t require simulation of the pituitary gland.

For GABA to produce the same effect, in theory, it would have to pass through the blood brain barrier to even reach the pituitary gland. Of course not much gets there, yet some muscle mass increase has been documented when GABA supplements are used. So what’s happening? It turns out that growth hormone has over 100 different forms that can float through the bloodstream at any given moment, a few of which GABA can interact with. So, when GABA supplements enter the bloodstream, these reactions can cause a slight increase in growth hormone production. The result can be increased muscle mass over time.

Now, let’s look at the potential side effects.

The terminology ‘side effect’ refers to any undesired result, which can be rather subjective. For example, say you took a GABA supplement in the hopes that it would reduce your anxiety. The current science strongly suggests that you’re most likely to remain anxious, albeit slightly more bulky, and wondering why you wasted your money on the stuff. If you took GABA to increase your muscle mass, then apparently there are no side effects. As for the brain itself, no side effects are known at this time, at least from the recommended dosages of 500 mg to over 1,000 mg per day. However, an appropriate and safe daily dosage has yet to be defined, at least by science.

Lesson Summary

When it comes to your health, ingesting medicinal supplements that are branded as ‘natural’ does not necessarily mean they are safe to take. GABA, one of these natural supplements, is a neurotransmitter (specific molecules or compounds) that is released in the synapses, which is the space where neurotransmitters flow between the neurons (the trillions of nerve cells in our brains). GABA, or gamma-aminobutyric acid, inhibits production of a new impulse, the opposite of glutamate, which initiates a new impulse in the postsynaptic neuron.

In the case of GABA being used as a supplement, it’s apparently safe to consume within the recommended dosages. However, the science so far has demonstrated that using GABA to reduce anxiety probably has little to no effect because the blood brain barrier blocks most of it from reaching the brain. On the other hand, you could experience some muscle mass increase by taking GABA supplements because GABA reacts with forms of growth hormone already in the bloodstream, thus the blood brain barrier is not an issue. Therefore, depending on the need, you’ll have to decide if GABA supplements are worthy of their claimed benefits.

Key Terms

Neurons communicate with one another

Neurons – nerve cells which can produce impulses

Synapses – tiny gaps between neurons

Neurotransmitters – molecules or compounds which are released by a neuron on one side of the synapse and float across the gap to communicate with the next neuron in line

Glutamate – one of the two major neurotransmitters in humans; it fits into corresponding receptor sites to initiate a new impulse in the postsynaptic neuron

GABA – gamma-aminobutyric acid, the other major neurotransmitter in humans; fits into receptor sites to prevent production of a new impulse

Learning Outcome

After watching the video, you should be able to:

Describe how neurons transmit information
Identify the purpose of each of the two major neurotransmitters in humans
Discuss the two uses of GABA supplementation and whether it is effective
Describe the side effects of GABA supplements

What is GABA?

It is now widely known as the main inhibitory receptor in the human cortex, but in recent years it has become a widely available food supplement in both Europe and the United States. GABA is considered to be a ‘dietary supplement;’ as such, it can be sold without evidence to support its efficacy. GABA is widely distributed in nature.

GABA is an inhibitory neurotransmitter of the nervous system. Image Credit: Molecular Arts / Shutterstock

What are the role and distribution of GABA?

GABA is distributed unequally in the brain. Its inhibitory effects result from inhibition of neuronal activity and synaptic plasticity. Although GABA’s primary function is as a neurotransmitter, it has the structure of an amino acid and is therefore referred to as an amino acid neurotransmitter. GABA is produced as glutamine in the diet is converted first to glutamate, then to GABA by glutamic acid decarboxylase. In adult brains GABA is inhibitory, whereas in the embryonic brain it is a well-established excitatory transmitter that exerts region-specific roles according to the developmental stage of the embryo.

Learning About GABA – Part 1Play

GABA receptors, agonists and modulators

Nearly half of all synapses of the brain express some kind of GABA receptor. GABAA receptors are widely but differentially distributed within the CNS and they can be activated by several GABA isosteres, which are compounds with the same number of atoms and electrons. There are 2 types of receptors that GABA can stimulate: GABAA and GABAB. GABAA receptors are ionotropic; on GABA binding, an associated ion channel that is permeable to the negatively charged chloride ions opens to hyperpolarize the membrane potential. This decreases the likelihood of the neuron firing an action potential.

GABAB receptors are metabotropic or G protein-coupled receptors. The predominant effect of GABAB stimulation is the opening of potassium channels. As with chloride, potassium influx results in hyperpolarization, which decreases likelihood that a neuron will fire an action potential.

GABAA also has allosteric binding sites for other substances referred to as GABA modulators. These are capable of increasing or decreasing the action of GABA; in its absence, they have no effect. Depending on their effect, they are classified as positive or negative allosteric modulators (PAMs and NAMs, respectively).

A prominent example of a class of GABAA receptor positive allosteric modulators is benzodiazepines. They facilitate the interaction between GABA and GABAA, therefore potentiating the GABA inhibitory effect. These types of drugs are commonly used is for sedative purposes.

Other positive modulators include barbiturates and alcohol. Negative modulators, by contrast, compete with the binding of a positive modulator at the same site. Flumazenil is one such example of a competitive antagonist; it is used to reverse benzodiazepine overdose.

Some drugs show off-target negative allosteric modulator effects. For example, fluoroquinolone antibiotics, antidepressants, and beta-lactam antibiotics can negatively modulate GABA. GABA agonists also produce the same effect as positive allosteric modulators; they culminate in the reduction of the neuronal signals in the user’s brain. GABA antagonists, in contrast, increase brain activity — examples include gabazine or bicuculline.

GABA and the blood-brain barrier

Historically, GABA has been thought to be unable to cross the blood-brain barrier (BBB), which throws into question the efficacy of GABA supplements to alleviate anxiety or improved sleep amongst other positive effects. However, the evidence to support GABA’s permeability is conflicting. several studies are unable to show that GABA crosses the BBB whereas others demonstrate its ability to do so.

According to an article published in Frontiers in Psychology (2015), the mechanism behind GABA supplements are unclear and further work is needed to establish the behavioral effects of GABA. The authors speculate that there is insufficient evidence to rule out the possible effect. Moreover, studies that have used GABA mimetics that do not structurally reflect the GABA molecule and delivered GABA through mechanisms that do not reflect user administration. Most notably, the permeability of GABA to the BBB has been confined to rodents.

Despite conflicting evidence for its entry into the CNS, GABBA may still affect the brain through the enteric nervous system, which contains many GABA receptors. The efficacy of GABA supplements is therefore confined to anecdotal evidence.

References

Moss, F.J., Imoukhuede, P.I, Just, H. & Lester, H.A. TRANSPORTERS | GABA Transporters: Structure, Oligomerization, Trafficking, and Pharmacology Determine Neuronal Excitability, Encycolpedia of Basic Epilepsy Research. (2009) doi: 10.1016/B978-012373961-2.00116-8

Goetz, T., Wulf, P., and Wisden, W. GABAA Receptors: Molecular Biology, Cell Biology, and Pharmacology. Encyclopedia of Neuroscience. (2009) doi: 10.1016/B978-008045046-9.01236-5

Sigel, E. et al. Structure, Function, and Modulation of GABAA Receptors. JBC. (2012) doi: 10.1074/jbc.R112.386664

Kinnersley, A.M 7 Turano, F.J. Gamma Aminobutyric Acid (GABA) and Plant Responses to Stress. Critical Reviews in Plant Sciences. (2000) doi: 10.1080/07352680091139277

Owens, D.f. & Kriegstein, A.R. Is there more to gaba than synaptic inhibition? Nature (2002) doi:10.1038/nrn919

Gamma-aminobutyric acid or simply GABA is a chemical compound from the group of amino acids that does not have proteins in its structure.

This is a substance of natural origin, synthesized in the human body from the amino acid glutamine. The first studies, during which aminobutyric acid was identified, were carried out back in 1954-1956. Then it was possible only to determine its presence in the central nervous system of a person. It was possible to synthesize the substance in question only in 1963.

The main task of this compound is that it inhibits the transmission of certain impulses and relaxes the nervous system.It helps a person return to a calm, stable state and get out of depression or stress faster.

Useful properties of gamma-aminobutyric acid (GABA)

GABA is one of the most important inhibitory neurotransmitters of the nervous system.It is widely used in medical practice, since it is an effective aid in the treatment of mental disorders, and also has a relaxing and sedative effect. The substance activates metabolic processes, saturates the brain with oxygen and improves blood circulation throughout the body.

Constant stress and anxiety, as you know, lead to a weakening of the immune system, they are also often accompanied by sleep disturbance, which in turn also negatively affects the functioning of the immune system.GABA helps reduce stress and promote a healthy immune response to stressors.

The compound plays an important role in ensuring a good night’s rest, it improves the quality of sleep, and lack of it is one of the main causes of insomnia.

In addition, it regulates motor activity, improves memory and thinking processes, and also has an anticonvulsant effect. Being one of the most important components of blood and brain, gamma-aminobutyric acid is able to improve blood supply to the brain, activate energy processes and increase the respiratory activity of tissues.In addition, it accelerates the utilization of glucose and helps to eliminate toxic metabolic products.

Speaking of other equally important effects that the product in question has on the body, the following can be distinguished:

• helps in the fight against vascular pathologies;

• normalizes blood pressure;

• improves liver function;

• relieves nervous tension;

• relieves negative stress symptoms;

• has a positive effect on the state of the nervous system as a whole;

• has a relaxing effect;

• speeds up the process of falling asleep;

• increases the body’s resistance to stressful situations;

• normalizes the work of the cardiovascular system;

• increases the ability to concentrate;

• Supports optimal brain function in old age.

<br />

Who needs additional intake of GABA

Most often, gamma-aminobutyric acid is used as an additional agent in the treatment of diseases such as epilepsy, arterial hypertension, endogenous depression, atherosclerosis.

It can also bring undeniable benefits for patients during the recovery period after head injuries. In addition, GABA will be able to help people experiencing problems with sexual function and those who often suffer from headaches and dizziness.

It is recommended to use the product additionally for babies who are lagging behind in development and for those who have disorders in the work of the speech apparatus.

What role does GABA play in the lives of athletes

For bodybuilders and people involved in various sports, this product is of particular interest. This is due to the fact that it helps to increase growth hormone or growth hormone, which in turn has an anabolic and fat burning effect. Due to the increased level of somatotropin, muscle gain is accelerated, strength indicators increase, and the process of burning subcutaneous fat is activated.

A very important advantage of supplements based on this component for athletes is that they help to fall asleep faster and deepen sleep.

Thus, the restoration of muscle fibers damaged during physical exertion occurs much faster and more efficiently. Among other things, the substance in question is able to prevent muscle cramps and reduce the level of cortisol or stress hormone, which enhances catabolic processes in muscles.

The main symptoms of GABA deficiency

People who are deficient in this compound cannot work productively during the day, and they also have problems sleeping, anxiety and unreasonable aggression.

Other signs of deficiency include:

• panic attacks;

• problems with concentration;

• persistent headaches;

• weak resistance to stress;

• inability to calm down;

• increased night sweats;

• constant fatigue;

• visual impairment.

The deficiency of this compound can be replenished either with the help of regular food products, or by supplementing the intake of GABA in the form of tablets, capsules or powder.As for food, a large amount of this substance is found in tomatoes, sprouted rice, eggplant, potatoes, peaches, kiwi, pumpkin, carrots. But, unfortunately, with the modern rhythm of life, not everyone manages to eat regularly and properly.

That is why many resort to the second option and include in their daily diet special complexes based on this component, which are rather quickly absorbed in the body, and then also quickly enter the tissues.

And the most popular dietary supplements from this category are the following:

• Solgar GABA – the product is presented by a popular American company of premium quality, the products of which are produced in glass jars for easy transportation and storage. The additive can be selected in different packaging in the form of capsules. The manufacturer has taken care of everyone’s health and needs, so the product is kosher, gluten-free and vegan-friendly.

• Gaba Now – this manufacturer from the USA presented several products from this category in its numerous assortment.Therefore, you can easily find what you need exactly. The company has a pleasant pricing policy and many satisfied consumers around the world.

GABA

GABA

GABA (Gamma-aminobutyrate or gamma-aminobutyric acid, GABA) is one of the most important mediators in the brain, which has a suppressive effect. It is an amino acid by nature. GABA in the human body induces sleep and eliminates mental agitation.

Gamma-aminobutyric acid has a property that is very important for athletes. This drug has a beneficial effect on the action of the excretory system. GABA stimulates the secretion and release of one of the most powerful anabolic hormones – growth hormone. Growth hormone (GH) is most abundantly released during two peaks: during deep sleep (noREM) and during extreme physical activity. The growth hormone itself is produced by the anterior pituitary gland. GABA when combined with resistance training increases the secretion of growth hormone.Thanks to this, our efforts give better results, and muscle adaptation is faster. Scientists have conducted various studies that have confirmed the positive effect of GABA on the secretory processes of the pituitary gland. This active neurotransmitter, when combined with intense strength exercise and adequate sleep, can intensify the results of recovery and muscle growth. The study, conducted by researchers from the University of Connecticut, analyzed the effects of taking GABA on 11 male bodybuilders, with a median age of 23.They did barbell squats because extreme exercise produces the highest growth hormone release. The load was 70% of the study participants’ maximum strength capabilities, and the workout lasted 90 minutes. Compared with the control group, those taking 3 g of GABA per day had a significant increase in the level of growth hormone in the blood. It also turned out that the bodybuilders taking part in the study also had increased levels of testosterone and IGF-1 (insulin-like growth factor).When gamma-aminobutyric acid is used under certain conditions (strength training), these hormones can cause muscle hypertrophy. GABA, as a neurotransmitter of the central nervous system, improves the quality of sleep, and it is at night that the largest amount of growth hormone is released. This component limits the effects of stressors and provides significantly deeper and more effective sleep. Due to this, the amount of synthesized growth hormone and its anabolic effect on the body are significantly increased.In addition, GABA produces an additional anabolic and anti-catabolic effects by reducing the release of cortisol, a stress hormone that has a damaging effect on muscle tissue. Gamma-aminobutyric acid inhibits the action of adrenocorticotropic hormone (ACTH) produced by the pituitary gland, which in turn stimulates the adrenal cortex to produce and secrete cortisol .

The recommended dose of GABA is 3-7 grams per day (up to 15 grams).It is better not to take it at the same time with protein and other proteins, as it is less absorbed.

Side effects of GABA include mild tingling in the face and neck, changes in heart rate and breathing. These side effects are not harmful to health, usually occurring at a dose above 4 g per day, but usually quickly disappear after a few days of use.

GABA can cause drowsiness, so it is sometimes taken before bed.

Almighty GABA and the Brain

GABA (gamma-aminobutyric acid or GABA) is an inhibitory neurotransmitter that has a calming and relaxing effect on the brain.It acts like the brakes in a car, where it slows down and / or pauses brain activity as needed to help us function better.

When we have a low level of this neurotransmitter , our brain “gasps”, overstimulating us with activity. Our gut microbiome plays an important role in the production of GABA and helps convert glutamine and glutamic acid to GABA. A disordered microbiome is the main cause of low GABA production (1, 2).

GABA activity in the brain

Functions of the GABAergic system in the central nervous system.

GABA, an inhibitory mediator, causes hyperpolarization of the postsynaptic membrane, resulting in decreased neuronal activity in the target cell. The widespread occurrence of GABAergic synapses indicates the importance of inhibition processes for the normal functioning of the central nervous system.

Experimental blockade of GABAergic transmission or its violation in pathological cases cause uncontrolled neuronal discharges – convulsions.The manifestations of epilepsy , parkinsonism and some other lesions of the extrapyramidal system are closely related to the violation of the GABAergic system.

The GABAergic system is involved in the formation of emotional behavior.

However, the role of GABA is not limited solely to suppression of excitation in the central nervous system. Tonic inhibitory inputs can transform the activity of target cells, providing spatial and temporal integration of excitatory inputs, that underlie the information processing mechanism .

Moreover, in neural networks, inhibitory interactions can be organized in such a way as to provide reverse inhibitory connections (recurrent inhibition), which underlies the formation of oscillatory activity. By controlling the temporal parameters of the discharges of many cells, inhibitory interneurons synchronize the activity of neural populations and even increase the effect of excitatory inputs.

And finally, despite the fact that in the adult brain, GABA performs the function of an inhibitory mediator, in the developing brain it provides excitatory processes, which is fundamentally important for the development of the nervous system.

GABA is synthesized from glutamate – an amino acid with the enzyme glutamate decarboxylase and pyridoxal phosphate – an active form of vitamin B6 as a key cofactor.
This process converts glutamate , which is the main excitatory neurotransmitter in the brain, into the main inhibitory neurotransmitter GABA (3, 4).

In most areas of the brain, GABA is too large a molecule to cross the blood-brain barrier (5).However, there are certain areas that have a permeable barrier, such as the periventricular nucleus of the hypothalamus, which is located in the 3-^m ventricle of the brain. GABA has been shown to affect brain activity in this region and help modulate the amount of human growth hormone released (6).

GABA is also an important part of the synthesis of the sleep hormone melatonin . It plays a key role in the conversion of serotonin to N-acetylserotonin , which is then converted to melatonin to stimulate sleep (7).Melatonin also plays a huge role in the body’s immune function.

Factors involved in lowering GABA levels

There are too many factors involved in lowering GABA levels to name them all. Here are just a few of the more common ones.

Gut microbiome: Dysbiosis

There is a growing body of research linking gut microbiome to neurological and mental health. Studies have shown that destruction of the intestinal mucosa, along with low levels of beneficial microorganisms such as lactobacilli and bifidobacteria, are associated with lower GABA levels, increased brain excitability and neurological inflammation (12).

These probiotics are required for the absorption and activation of B6 , which is a critical cofactor in the conversion of excitatory neurotransmitter glutamate to GABA.

Without adequate activated B6, we get the excitotoxicity of glutamate and an increased risk of anxiety, seizures, epilepsy, depression, dementia, and Alzheimer’s disease (13, 14).

Antibodies to Glutamate Decarboxylase

In the previous section, we discussed how the body converts Glutamine to GABA using the enzyme glutamate decarboxylase and an activated form of vitamin B6.Some people have elevated antibodies (autoimmunity) to the enzyme glutamate decarboxylase. This is especially common in people with epilepsy and other seizures (15).

Another study showed that this condition occurs in people with cerebellar ataxia, muscle stiffness syndrome, type I diabetes, drug-resistant epilepsy, balance problems, and others (16). In these cases, the following protocols are especially helpful for reducing inflammation and autoimmunity.In addition, these people may need high doses of supplemental gamma-aminobutyric acid (GABA).

Low in zinc, vitamin B6, magnesium, taurine and glutamine

Amino acid L-glutamine is the most abundant amino acid in the body and is a precursor to the production of GABA. Glutamine is first converted to glutamate, which is the key to good concentration, brain energy, learning, and memory.

This is important, but we need the right percentage of glutamic acid, which must then be converted to GABA, or we risk overstimulating our neuronal cells.The next step in converting glutamate to GABA relies on the activated form of vitamin B6, pyridoxal 5-phosphate (P5P).

In addition, the amino acid taurine increases the bond and productivity of P5P and promotes the production of GABA. There are studies that have shown that taurine deficiency can lead to anxiety (17).

Zinc enhances GABA release, helping activate P5P and stimulate glutamate decarboxylase activity (18).Both B6 and zinc are also required for the production and use of other neurotransmitters such as serotonin , dopamine, norepinephrine, epinephrine, and histamine.

Magnesium is important for the binding and activation of GABA receptors. Without adequate magnesium , we cannot effectively activate GABA receptors and use it effectively ( 19 ). Magnesium deficiency is extremely common in over 80% of women and 70% of men, and thus supplementation for most will dramatically affect GABA activity.

Chronic stress and adrenal fatigue

Chronic stress increases the levels of cortisol, norepinephrine and adrenaline in the brain and body. It also helps the body produce more excitatory glutamate and decreases GABA production (8).

Too much glutamate in the brain causes the brain cells to over-excite. In addition, an increase in stress hormones increases cellular activity and induces an overproduction of free radicals that damage brain cells and further reduce normal GABA production (9).

Over time, when a person is in a prolonged stressful state, he rearranges his brain cells and has a functional deficiency in the production of GABA (10). This is where lifestyle interventions and a GABA supplementation protocol strategy, undertaken over a period of time, greatly help rewire the brain to efficiently produce and use GABA again.

Poor sleep

Lack of quality sleep is a chronic stress for the body and increases the production of stress hormones.This causes the same mechanisms as described above. The question was which came first: was stress and low levels of GABA and melatonin causing poor sleep, or was poor sleep causing chronic stress and low levels of GABA and melatonin.

In any case, this is a truly vicious cycle, when several unsuccessful nights of sleep in a row can lead to brain restructuring and functional deficiency in the production of GABA (11). This is yet another case where using lifestyle strategies and supplementation over a period of time is extremely beneficial in retooling the brain to efficiently produce and reuse GABA.

Unstable blood sugar

Impaired blood sugar regulation is a significant stressor in the brain and destroys the blood-brain barrier, which is designed to protect the brain from oxidative stress, infectious microbes, toxins and chronic inflammation.

Hypoglycemia or low blood sugar causes partial starvation of brain tissue, which increases stress hormone levels and increases the permeability of the blood-brain barrier for more nutrients.But it also allows more toxins and free radicals to attack brain tissue, causing elevated stress hormones and glutamate release.

In addition, high blood sugar causes insulin resistance in the brain and functional starvation when glucose is sufficient but we cannot get it to the brain for further use. In this case, this leads to the opening of the BBB and excessive oxidative damage to the brain with increased levels of stress hormones and the release of glutamate.

Supplements to increase the level of GABA

Supplements to increase the level of GABA

Magnesium: Supplemental magnesium helps to increase the level of GABA. The most effective form of magnesium for increasing GABA is called magnesium L-threonate. I recommend taking 1-2 grams – 1-2 times a day.

Vitamin B Complex: B6 deficiency can cause low levels of GABA. I usually recommend a complex supplement with active forms of B vitamins.

Probiotics: In particular, the addition of probiotics containing various strains of lactobacillus and Bifidobacterium helps to increase GABA levels. I recommend taking 30-100 billion CFU daily.

GABA: Taking additional GABA can be very effective. It is not believed to cross the blood-brain barrier, however, in most people with low GABA levels, the blood-brain barrier is impaired and they respond very well to additional GABA.I recommend taking 100-200 mg 1-2 times a day.

L-Glutamine: L-Glutamine supplementation can be very effective in maintaining GABA levels. I recommend starting with 4-5 grams to see how your body can handle it, and gradually hang up to 10-12 grams.

If you notice an increase in irritability, headache, or anxiety, you may have deficiencies in B6 and / or zinc . Try adding them while lowering your L-glutamine levels, then try L-glutamine again.

Taurine: is a precursor to the amino acid GABA and has a similar structure but less. It helps activate GABA receptors in the brain. I use 300-600 mg 1-2 times a day.

L-Theanine: is a naturally occurring, biologically active free form amino acid that provides relaxation support. L-theanine improves GABA production and induces a relaxed state of mind without causing drowsiness. I recommend 50-100 mg 1-2 times a day.

Valerian, Kava, Chamomile, Lavender, Peppermint and Passionflower: These herbs help improve the production and use of GABA in the brain.You can drink herbal tea with them or apply essential oils to the body, use in an Epsom salt bath or diffuser to breathe in these supportive compounds.

Sources:

[su_expand more_text = ”Show more links” less_text = ”Show fewer links” hide_less = ”yes”] Sources:
1. Galland L. The Gut Microbiome and the Brain. Journal of Medicinal Food. 2014; 17 (12): 1261-1272.
2. Evrensel A, Ceylan ME. The Gut-Brain Axis: The Missing Link in Depression.Clinical Psychopharmacology and Neuroscience. 2015; 13 (3): 239-244.
3. Petroff OA. GABAA and glutamate in the human brain. Neuroscientist. 2002 90 100 4. Dec; 8 (6): 562-73. Review. PubMed PMID: 12467378
5. Kuriyama K, Sze PY. Blood-brain barrier to h4-gamma-aminobutyric acid in normal and amino oxyacetic acid-treated animals. Neuropharmacology. 1971 Jan; 10 (1): 103-8. PMID: 5569303
6. Powers ME, Yarrow JF, McCoy SC, Borst SE. Growth hormone isoform responses to GABAA ingestion at rest and after exercise.Med Sci Sports Exerc. PMID: 18091016
7. Balemans MG, Mans D, Smith I, Van Benthem J. The influence of GABAA on the synthesis of N-acetylserotonin, melatonin, O-acetyl-5-hydroxytryptophol and O-acetyl-5-methoxytryptophol in the pineal gland of the male Wistar rat. ReprodNutr Dev. PubMed PMID: 6844712
8. Bremner JD. Traumatic stress: effects on the brain. Dialogues in Clinical Neuroscience. 2006; 8 (4): 445-461.
9. Alekseenko, A.V., Kolos, V.A., Waseem, T.V. Glutamate induces formation of free radicals in rat brain synaptosomes.BIOPHYSICS (2009) 54: 617.
10. Liu ZP, Song C, Wang M, He Y, Xu XB, Pan HQ, Chen WB, Peng WJ, Pan BX. Chronic stress impairs GABAergic control of amygdala through suppressing the tonic GABAA receptor currents. Mol Brain. 2014 Apr 24; 7:32. PMID: 24758222
11. Winkelman JW, Buxton OM, Jensen JE, et al. Reduced Brain GABAA in Primary Insomnia: Preliminary Data from 4T Proton Magnetic Resonance Spectroscopy (1H-MRS). Sleep. 2008; 31 (11): 1499-1506.
12. Kelly JR, Kennedy PJ, Cryan JF, Dinan TG, Clarke G, Hyland NP.Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders. Frontiers in Cellular Neuroscience. 2015; 9: 392.
13. Hill JM, Bhattacharjee S, Pogue AI, Lukiw WJ. The Gastrointestinal Tract Microbiome and Potential Link to Alzheimer’s Disease. Frontiers in Neurology. 2014; 5:43.
14. Burbaeva GSh, Boksha IS, Tereshkina EB, Savushkina OK, Prokhorova TA, Vorobyeva EA. Glutamate and GABAA-metabolizing enzymes in post-mortem cerebellum in Alzheimer’s disease: phosphate-activated glutaminase and glutamic acid decarboxylase.Cerebellum. 2014 Oct; 13 (5): 607-15.
15. Stagg CJ, Lang B, Best JG, McKnight K, Cavey A, Johansen-Berg H, Vincent A, Palace J. Autoantibodies to glutamic acid decarboxylase in patients with epilepsy are associated with low cortical GABAA levels. Epilepsia. 2010 Sep; 51 (9): 1898-901.
16. Vianello M, Tavolato B, Giometto B. Glutamic acid decarboxylase autoantibodies and neurological disorders. Neurol Sci. 2002 Oct; 23 (4): 145-51. PMID: 12536283
17. Kong WX, Chen SW, Li YL, Zhang YJ, Wang R, Min L, Mi X.Effects of taurine on rat behaviors in three anxiety models. Pharmacol Biochem Behav. Feb; 83 (2): 271-6. Epub 2006 Mar 15. PubMed PMID: 16540157
18. Ebadi M, Wilt S, Ramaley R, Swanson S, Mebus C. The role of zinc and zinc-binding proteins in regulation of glutamic acid decarboxylase in brain. Prog Clin Biol Res. 1984; 144A: 255-75. PubMed PMID: 6328536
19. Möykkynen T, Uusi-Oukari M, Heikkilä J, Lovinger DM, Lüddens H, Korpi ER. Magnesium potentiation of the function of native and recombinant GABAA receptors.Neuroreport. 2001 Jul 20; 12 (10): 2175-9. PMID: 11447329 [/ su_expand]

Gamk (gamma-aminobutyric acid, gaba)

GABA
(gamma-aminobutyric acid, GABA) is
the main inhibitory neurotransmitter
CNS, whose receptors are widely
common in the structures of the head
brain, in almost all neuronal
groups [Fagg G.E., Foster A.S. 1983]. Gamma-aminobutyric
acid (GABA) is among the most
important neurotransmitters of the brain, it is
inhibitory mediator of the central nervous system.

Gamma-aminobutyric
acid synthesized only in
Nervous System Glutamic
acid by means of glutamate decarboxylase.
It is found in the central nervous system everywhere, in
very different concentrations. When
electrophoretic application
gamma-aminobutyric acid has
usually braking action.
There is evidence that this acid
participates in presynaptic inhibition
as a mediator in axo-axonal
synapses. Some convulsive poisons (
alkaloid bikuculin, picrotoxin)
turned out to be specific antagonists
this acid.

Introducing
natural defense mechanism, GABA
restricts arousal stimulus
as presynaptically – through
GABAB- receptors, functional
related to potential-dependent
calcium channels presynaptic
membranes, and postsynaptically through
GABAA receptors
(GABA-barbiturate-benzodiazepine receptor
complex), functionally related to
voltage-dependent chlorine channels .

Radioimmunological
research has especially confirmed
widespread in structures
brain GABAA receptors.The largest of them
density is determined in the temporal and
frontal cortex, hippocampus, almond
and hypothalamic nuclei, black
substance, gray matter around
aqueduct, cerebellar nuclei. Some
to a lesser extent receptors are represented
in caudate nucleus, shell, thalamus
, occipital cortex, pineal gland.

Activation
postsynaptic GABAA receptors
leads to hyperpolarization of cellular
membranes and inhibition of the excitatory
impulse caused by depolarization.
All three subunits of the GABAA receptor
(alpha, beta and gamma) bind GABA,
although the highest affinity
binding is noted with the alpha subunit.Barbiturates interact with alpha
and beta subunits; benzodiazepines
only with a gamma subunit. Shown
that the binding affinity of each of
ligands increases if in parallel
others interact with the receptor
ligands.

Main
physiological role of GABA – modulation
activity of the main excitatory
neurotransmitter glutamate, creating
stable balance between exciting
and brake systems . Exist
certain proportions between
representation of glutamate receptors
and GABA receptors in different areas
brain.The most sensitive neurons
to ischemia, along with the powerful glutamate
aspartate excitatory input on
dendritic tree have many
GABAergic terminals on bodies
cells.

In the first
experimental cerebral seconds
ischemia occurs instant release
glutamate and GABA from presynaptic
terminals [Green A.R., Cross A.J. 1992]. However, in
the first 4 hours there is a failure
GABAergic inhibitory neurotransmission
[Gusev E.I., Skvortsova V.I. 1995, Gusev
E.I., Skvortsova V.I. 1999, Gusev E.I., Skvortsova V.L.
2000]. Stimulation of GABAA receptors in
experiment allows you to regulate
activity of calcium glutamate
excitotoxic cascade [Green A.R.,
Cross A.J. 1992].

Long
time it was believed that this amino acid
exclusively associated with synaptic
braking. But it turned out that in the early
stages of brain development GABA mediates
predominantly synaptic arousal
… In the adult brain, the excitatory function
GABA is retained only partially, yielding
place of synaptic inhibition [
Ben-Ari ea 2002, Ben-Ari ea 1989, Taira ea 1997].

Glutamate
(glutamic acid, GLUTAMATE, GLU)

Glutamate
is the main aphrodisiac
neurotransmitter in the central nervous system of mammals.
It is involved in a large number of neuronal
and glial processes. In addition to
recognized role of this mediator in
brain in higher cognitive
learning and memorization processes can
note the participation of this ligand as
neurotoxic agent in development
many neurodegenerative diseases
…

Mid
80s of the last century believed that
glutamate realizes its effects through
a group of ionotropic membrane receptors –
channels (ligand-dependent ionic
channels): NMDA receptors, AMPA receptors and
kainate receptors.

However, in
a series of studies started in the middle
80s and continuing to this day, there were
it has been shown that glutamate can activate
phospholipase C (PLC), which leads to
the formation of inositol phosphate and
diacylglycerol in neurons like this
occurs when some
receptors coupled to G-proteins (
Sladeczek, F. et al., 1985). Search for a receptor,
mediating a similar effect of glutamate,
led to the discovery of a protein, now
time known as metabotropic
glutamate receptor subclass 1a (
mGluR1a).

L-glutamic
acid; alpha-aminoglutaric acid
Like. mass 147.1 C5H9O4N COOH-Ch3-Ch3-CH h3COOH Colorless
needle-like crystals.

Soluble
in water, worse in ethanol and methanol. T pl.
247-249 degrees C at 25 degrees C at 5 M
HCL, [alpha] = + 31.8. pK 2.19, 4.25 and 9.67., IEP (pI) = 3.22.

Glutamic
electrophoretic acid
application has a stimulating
action. Since glutamic acid
found in the central nervous system throughout, very likely
that she is not only a predecessor
gamma-aminobutyric acid, but other than
Moreover, it itself acts as a mediator.

UTP + ATP + GLN = GLU + ADP + Pi + CTP

Glycine
(glycine): general information

Glycine –
inhibitory neurotransmitter in mechanisms
acute cerebral ischemia.

Amino acid
glycine serves as a mediator in some
cases of postsynaptic inhibition
in the spinal cord. Specific
the glycine antagonist is strychnine,
amino acids

Traditionally
it was believed that glycine (glycine) exhibits
neurotransmitter properties at the level
spinal cord, medulla oblongata
and the bridge, mainly from
segmental interneurons and
propriospinal systems and inhibiting
by means of axo-dendritic and
axo-axonal contacts motoneurons
[Curtis D.R., Hosli L. 1968, Hammerstad J.F., Murray J.E. 1971,
Hopkin J., Neal M.J. 1971, Osborne R.H., Bradford H.F. 1973].
Later, the role of glycine as
inhibitory neurotransmitter practically
in all parts of the central nervous system. In the brain
high density of glycine receptors
found not only in trunk structures
, but also in the cerebral cortex, striatum
, nuclei of the hypothalamus, conductors from
frontal cortex to hypothalamus, cerebellum
… It was concluded that GABA and glycine
are equivalent neurotransmitters
providing protective braking
in the central nervous system, the role of which increases in
conditions of increased glutamate release
[Fagg G.E., Foster A. C. 1983, Mayor F., Valdivieso F. 1991].

Inhibiting
glycine exhibits properties by
interactions not only with their own
glycine receptors, but also with
GABA receptors [Fagg G.E., Foster A.S. 1983,
James T.A., Starr M.S. 1979, Mayor F., Valdivieso F. 1991]. Together
so it has been experimentally proven that
glycine in submicromolecular
concentrations is necessary for normal
functioning of glutamate
NMDA receptors [Johnson J. W., Ascher P. 1987]. Activation
NMDA receptors is possible only if
binding of glycine to their specific
(insensitive to strychnine)
glycine sites, i.e.that is, glycine is
their co-agonist. Under normal conditions
in vivo, the usual concentrations of endogenous
glycine completely bind sites
glutamate receptors. [
Henderson G., Johnson J. 1990, Johnson J. W., Ascher P. 1987, Kemp
J.A., Leeson P.O. 1993, Kleckner N.W .. Dingleciine R. 1988,
Park C.K., Nehls D.G. 1988]. Potentiating action
glycine on NMDA receptors is manifested in
concentrations below 0.1 μmol, and concentrations
from 10 to 100 μmol completely saturate
glycine site [Chizhmakov I.V., Kishin N.I. 1989].
Administration of high concentrations of glycine
(100 μmol and 1 ml mol) to rats under conditions
lack of oxygen does not cause
long-term modulation of activity
NMDA receptors in the hippocampus [Jones M.G.,
Szatkowski M.S. 1995]. Confirmation received,
that increased concentrations of glycine,
which occur during ischemia (10-100
ml mol), do not activate NMDA-induced
depolarization in vivo and, therefore, does not
increase excitotoxicity [
Obrenovitch T.P., Hardy A.M. 1997, Obrenovitch T.P., Urenjak J. 1994
]. Interestingly, the introduction to animals
high doses of glycine or some
agonists (1-amino-1-carboxycyclopropane
, which is an almost complete agonist,
and D-cycloserine having 40-60%
efficiency of glycine) has
anticonvulsant action [Lapin I.P. 1981
, Peterson S.L., Boehnke I.E. 1989, Peterson S.L, Schwade N.D. 1993
, Scolnick P., Marvizon J. 1989, Stark L., Peterson S.L. 1990, Toth
E., Lajtha A. 1983, Tricklebank M.D., Saywell K. 1990], and
enhances the effects of antiepileptic
funds [Peterson S.L. 1991]. Such influence
glycine and its agonists would be
impossible if the main mechanism
neurotransmitter was the activation
glutamatergic systems.

Along with
neurotransmitter glycine possesses
also a general metabolic effect,
binds low molecular weight toxic
products (aldehydes, ketones), in large
quantities formed in the process
ischemia [Lavretskaya E.F. 1985, Meister A. 1957,
Williams R. 1963]. In an experiment on rats with
focal forebrain ischemia
injection of glycine at a dose of 20 mg / kg (during
the first 2 hours after surgery and then 1 time
per day for 9 days) was accompanied by
significant increase in concentration
glycine in the brain tissue (in the striatum – on
63%, in the parietal cortex – by 45%), reliably
increased the GABA turnover rate as
in the ischemic zone and in the surrounding tissue
compared to the control group
animals [Davalos A., Naveiro J. 1996]. On the background
the use of glycine showed a significant
decrease in product concentrations
oxidative stress in the ischemic zone, which
accompanied by rapid normalization
behavior and conditioned reflexes in rats
[Raevsky K.S., Romanova G.A. 1997, Romanova
G.A., Kudrin V.S. 1995]. Effective
action of glycine through receptor
zones, which significantly expands it
therapeutic possibilities. After 10
min after application labeled with tritium
glycine on the conjunctiva of the eyeball,
intranasally, on the mucous membrane
cheeks by scintillation spectrometry
recorded its increased consumption
in different brain structures and
cerebrospinal fluid [Badalyan
L.O., Skvortsov I.A. 1986, Raevsky K.S.,
Romanova G.A. 1997]. Applying glycine to
the conjunctiva of the eyeball is accompanied
increasing its concentration to
maximum in the first 30 minutes in visual
cross and after 2 hours – in the visual
zone of the crust [Badalyan L.O., Skvortsov I.A.
1986].

Main
active ingredient of pharmaceutical
glycine preparation is an amino acid
glycine, pharmaceutical carrier –
methylcellulose (0.5-2.0 wt%). Research
action of glycine in healthy volunteers
and a limited number of patients with
various neurological pathologies
demonstrated its complete safety
and good tolerance [Komissarova
AND.A., Gudkova Yu. A. 1992]. Being natural
brain metabolite, glycine did not show
toxicity even at doses over 10 g / day.
The only side effect of the drug
may be considered light sedation. A drug
glycine in doses of 300-600 mg / day has
anti-stress and nootropic effects [
Komissarova I.A., Gudkova Yu.A. 1992].

Histamine:
general information

Interaction
antigen with fixed IgE leads
to the release of inflammatory mediators
– histamine, leukotrienes, cytokines
and enzymes.

Histamine,
released during the activation of obese
cells and basophils, causes a variety of
changes in the cardiovascular system,
respiratory organs, gastrointestinal tract and skin:

– Reduction
smooth muscles of the bronchi.

– Edema
the mucous membrane of the respiratory tract.

– Increase
production of mucus in the airways,
contributing to their obstruction.

– Reduction
smooth muscles of the gastrointestinal tract (tenesmus, vomiting, diarrhea
).

– Decline
vascular tone and an increase in their
permeability.

– Erythema
, urticaria, angioedema caused by
increased vascular permeability.

– Decline
BCC due to decreased venous return.

At the beginning
80s H3 receptors were discovered.
It is shown that they are, by the mechanism of negative
feedback regulate synthesis and
secretion of histamine.

Histamine
found in some types of fish.

Peptides
neuroactive

Molecules
neuroactive peptides represent
more or less long chains
amino acids.It is assumed that
a substance that serves as a mediator in
primary afferent fibers in the dorsal
the brain is a neuroactive peptide.
Some of the neuroactive peptides
are neurohormones, i.e.
substances that are released from
nerve cells and then transferred
blood flow to their targets (not
neurons). These peptides include
liberins (releasing hormones), which
act on the adenohypophysis, antidiuretic
hormone (vasopressin) and oxytocin,
which are synthesized in the hypothalamus
and are stored in the neurohypophysis.

Another
a group of peptides affects activity
neurons not through synapses,
and being present as hormones,
for example, endorphins. Such peptides
called neuromodulators.

Serotonin
– mediator of allergic reactions

Serotonin
– a tryptophan derivative – is
one of the main neurotransmitters
central nervous system.
Pathogenetic effect on the body,
similar to histamine, (see “Histamine
– mediator of allergic reactions “)
also has serotonin.In man
activity of this compound is observed
only in relation to platelets and cells
small intestine. Serotonin refers
to inflammatory mediators. Role of Serotonin
in allergic reactions immediately
type is negligible. Serotonin
released from platelets when they
aggregation and causes a short
bronchospasm.

Carcinoids
most often secrete serotonin. how
shown in fig. 95.2, substrate for
the synthesis of serotonin is tryptophan,
which tumor cells invade
from blood.Carcinoid is able to recycle
up to half of all tryptophan supplied
with food. As a result, tryptophan can
not enough for the synthesis of proteins and nicotine
acid (vitamin PP). Therefore, in patients
with multiple metastases often
there are symptoms of protein
insufficiency and pellagra.

Serotonin
stimulates secretion and suppresses
absorption in the intestine, and also enhances
peristalsis. It is believed that exactly
high serotonin levels serve
cause of diarrhea with carcinoid
syndrome.In addition, serotonin stimulates
fibroblast proliferation and formation
collagen fibers, therefore
it can trigger or accelerate fibrosis
peritoneum and endocardium.

Excessive
the secretion of serotonin alone is insufficient
for hot flashes. In pathogenesis
vasomotor disorders take
many peptide hormones and
monoamines, and in different patients their
the ratio may not be the same.

Refers to
among the most important neurotransmitters
brain. Serotonin may play a role
link between leptin secretion
and suppression of the secretion of neuropeptide Y
…

Neuropeptide
Y

Hypothalamic
neuropeptide Y is a powerful stimulant
food activity. Leptin suppresses
synthesis or secretion of neuropeptide Y.
Serotonin may play a role
link between leptin secretion
and suppression of neuropeptide secretion
Y.

Excessive
secretion of neuropeptide Y in the funnel nucleus
– one of the possible causes of hypothalamic
obesity. Neuropeptide Y enhances
food consumption, because it causes hunger:
feeling of hunger, acting on hypothalamic
the center of satiety and the center of hunger.Besides
Moreover, neuropeptide Y lowers the sympathetic
and increases parasympathetic tone, and
also interferes with sexual function.

Endorphins
and beta-lipotropin fragments: General
information

(
Endorphins and Beta-Lipotropin fragments)

Opioid
peptides originally isolated from
brain, and then found in
many parts of the nervous system. Communicate
with the same receptors as exogenous
opiates (eg morphine, promedol).
Are among the most important
neurotransmitters of the brain.Violation in
release of endorphins may lie
at the heart of chronic pain syndromes
…

Spectrum
the action of endorphins is usually less
representative than for enkephalins
, however, the role of
endorphins in the motivation of alcoholic
behavior, nociceptive reactions,
under stress and in the regulation of circadian
processes. (Central and Peripheral
Endorphins: Basic and Clinical Aspects, 1984; Stefano G. et al.,
1994, Criscuolo M. et al., 1994, Ekman A. et al., 1994, Wiedennann
C.et al., 1994, Hara S. et al., 1995).

Proopiomelanocortin:
general characteristic

A number of peptide
pituitary hormones and neuropeptides,
such as adrenocorticotropin (ACTH
), alpha melanocyte stimulating hormones
, beta melanocyte stimulating hormones
and gamma melanocyte stimulating hormones
(MSH), beta-lipotropin and gamma-lipotropin
(LPG) and beta endorphins come from
a common precursor protein called
proopiomelanocortin (POMK). (fig.
45-7bx).

Proopiomelanocortin
is central to regulation
physiological homeostasis of the body
…Spectrum of action of peptides – derivatives
proopiomelanocortin – in the body
very wide. They control
processes of normal development, behavior
, memory, sleep, emotional and
physiological response to stress (
Smith A.I. ea, 1988; Imura H.ea, 1985; Chastrette N. ea, 1990).
POMA peptide derivatives can
act as neuromodulators and
neurotransmitters of the central nervous
system (central nervous system) (Tiligada E. ea, 1990), and the violation
their normal synthesis and processing
can lead to stress
dependent diseases and psychosomatic
human syndromes (N.P., 1990
).

90,000 Sleep and your health 9,0001

Today we will talk about brain activity with Elena BARANOVA , a renowned professor, an international expert in health genomics and personalized medicine, a member of the World Council of Anti-Aging Medicine, the creator of individual anti-aging programs and gene regulation drugs, who is actively involved in teaching, research and consulting work. The topic of our conversation is how to maintain strength, efficiency and good mood in winter.

Of course, the solution to this question begins with the quality of sleep. What health problems do you have if you have poor sleep? Various forms of fatigue develop, then the combustion syndrome – burnout, but there is also a disruption in the work of internal organs – the intestines, liver, since chronobiologically their recovery occurs at night. If we do not sleep, then the functions of these organs begin to suffer. In addition, weight regulation is directly related to sleep quality. People who sleep enough find it easier to lose weight while recovering.First of all, you need to establish sleep, and then the body begins to release kilograms. Particular attention should be paid to this for those who are over 35.

Elena, how does the season affect sleep?

Like various living organisms and plants on Earth – and we are not so different – we also adapt to the rhythms of the Sun, and many processes in our body go according to planetary processes, no matter how strange it sounds.

So activity slows down in winter?

Short daylight hours create a certain difficulty, since the brain is used to rest and recover with a decrease in light.Yes, the active work of the body slows down. Moreover, in winter, the production of both hormones and neurotransmitters of the brain decreases, and, of course, our life becomes more complicated with this. You have heard complaints many times and you yourself have felt a lack of energy in the winter. People often say, “I can’t get up in the morning.”

How to make it so that you do not depend on it and be able to recover as much as possible?

In the first place, and this applies to all our health, we put sleep and its quality. In my professional experience, people usually don’t know much about this.Many people either try to drink extracts of any plants, or take melatonin everywhere, but this raises a huge problem. The reason is the widespread opinion – someone somewhere heard that melatonin restores sleep.

First, let me tell you that our sleep period is divided into three fundamentally different phases. The first is the phase of falling asleep, the second is the middle of the night, and the third is the morning rise. And each of the phases is associated with its own problems. To begin with, in order to correctly set the correction and start sleep recovery, you need to figure out at which of the three stages you have difficulties.It always amazes me that usually few people know that melatonin is a hormone. I repeatedly hear philistine conversations: “Oh, you can’t drink hormones, it’s scary, it’s bad.” But it is worth asking the person the question: “Do you take melatonin?” In response, I hear: “Yes, of course.” “Do you know what a hormone is?” And people are genuinely surprised. Melatonin, the hormone responsible for the first phase of sleep, is produced in the body from 12 am to 2 am, and, accordingly, if you go to bed systematically late, you skip this phase.Or if you are in a state of overexcitation and cannot sleep, you also skip this phase in the production of melatonin.

What other functions does this hormone have?

It has many different functions, including melatonin, which has anti-cancer and antidepressant effects. The most important and insidious mistake is melatonin overdose. Here I want to emphasize that the maintenance dose is 0.5 mg, the corrective dose is 1 mg.If you have special circumstances and you need, say, to fly far, then depending on the body weight, you need to take from 2 to 4 mg, but a maximum of 1 -3 days.What do I see in practice? People drink melatonin on the principle that the higher the concentration, the better. And they drink it at 4-5 mg for several years. I have patients who have experienced severe sleep and health disorders due to melatonin overdose, but they did not even know about it.

Why is an overdose of melatonin dangerous?

The dream is shortened, becomes very short and very deep and, as the people say, bad. Waking up, a person does not understand what is happening to him, he needs some time to come to his senses.Moreover, waking up from such a dream in the middle of the night, a person can no longer fall asleep. Such a short nap is a consequence of an overdose of melatonin. It’s not hard to guess what people with these symptoms are doing – instead of stopping drinking melatonin, they drink even more. I had to take patients out under a drip due to melatonin intoxication.

At our Center, we conduct research and measure the level of melatonin. 39, a maximum of 40 units of melatonin content is normal.But I have seen indications of melatonin intoxication up to 900 units and above. This is really dangerous.

What happens in case of an overdose of melatonin?

Our hormones work on the principle of synergetics and antagonism – that is, they are either “friendly” or “not friendly” with each other. Melatonin is an antagonist of cortisol, the most important hormone of strength and endurance in our body. Melatonin in large quantities begins to suppress it. The situation is familiar: a person cannot get up in the morning, drinks melatonin, and still sleeps a little.And what does he do? Increases the dose. We ask you to be careful with melatonin. It is best consumed in summer, on long daylight hours. For example, in St. Petersburg, my good friend Professor Vladimir Anisimov, who, in fact, belongs to the “palm” in the discovery of melatonin and working with it, always regularly takes this hormone for two months of white nights – in May and June. And she strongly recommends it to everyone. This is logical, on white nights the sleep phase completely drops out from 12 o’clock at night to 2 o’clock in the morning.But, regardless of the white nights, there is a certain category of people who work very hard. I know those who systematically sleep from 2 to 5-7 in the morning, that is, they completely lose the synthesis of melatonin, which is responsible for the antidepressant state, anti-stress, recovery and anti-cancer effects.

How to find the middle ground?

In order not to be mistaken, it is best to conduct a survey and then select, if necessary, melatonin in the optimal dosage. Also, if you are over 40 years old, you have not previously taken melatonin and you have difficulty falling asleep or you go to bed late, then taking melatonin 0.5 – 1 mg before bed for 1-3 months is suitable for you.

The next big and common problem is systematic waking up around 3-5 in the morning. These sleep disorders are not related to melatonin. Behind this is an increase in anxiety and a decrease in an important recovery neurotransmitter called GABA or GABA – gamma-aminobutyric acid. In our time of general stress, I see the largest deficits in the population for this GABA parameter. Anxiety grows in people and this neurotransmitter is burned very quickly. It is important that the anti-anxiety neurotransmitter GABA has a protein structure.This means that for its production, a sufficient amount of protein is needed in the diet, otherwise it will not be produced. At my institute, a special drug “Gabadzhen” has been developed to correct increased anxiety and related sleep disorders. And this is one of the most popular drugs precisely because the deficiencies in this metabolic process are high.

What does the neurotransmitter GABA itself contribute to?

GABA is the most important resource for our health. This neurotransmitter relieves chronic anxiety, due to which sleep is corrected, debilitating sleep deprivation disappears, general anxiety decreases, and concentration and performance improve.In certain cases, cardiac interruptions decrease – tachycardia and palpitation. In my practice, there were patients who were offered to undergo heart surgery, but from the moment the correction for the restoration of GABA began, their normal heart rhythm was restored.

Today, most live in a state of chronic anxiety – 24 hours a day we are plugged into an outlet with phones, gadgets, etc. When there is no new SMS, messages, e-mails, a person begins to feel uncomfortable.(In parentheses, I note that today there are whole electromagnetic detoxification, when people are kept without access to the Internet / phones for some time.) Addiction to gadgets and phones is a severe modern syndrome that leads to the depletion of our neurotransmitters and a decrease in the efficiency of the brain, which does not manages to recover.

What else is characteristic of waking up around 3-5 o’clock in the morning?

There is a syndrome of “black thoughts” – a person wakes up at night, and hypertrophied stories begin to spin in his head – everything is bad, terrible, which is exhausting even more.Then after 5 o’clock in the morning he falls asleep, and in the morning everything does not look so bad. What does this mean? First of all about GABA deficiency, melatonin won’t help here.

What is the characteristic of the third phase of sleep – waking up?

When it’s dark outside, our fatigue problems are exacerbated, and this is especially painful. It is very difficult to get up in the morning for people with serotonin deficiencies – it is he who is responsible for easy awakening. In fairness, I must say that he is not alone in responding, there is still a mass of hormones – both the thyroid gland and the adrenal glands.But since today we are not talking about hormones, but about neurotransmitters, let’s dwell on serotonin – one of the most important sources of good mood, easy lift, joy of life.

Serotonin deficiency leads to severe loss of strength, up to depressive states, in addition, contributes to the development of increased appetite in the afternoon, towards evening. Especially in the evening hours, we are drawn to sweets, buns, because the production of serotonin starts just after 6 pm, and, accordingly, its lack manifests itself precisely at these hours.Those who go to bed early are less prone to this problem. We have developed special approaches to correct serotonin at our institute. It is important to stimulate its production 2 times a year – from mid-October to December inclusive, then, adjusted for the climate – from February to mid-April. It is very important to activate the synthesis of serotonin in November and March, since the body is most weakened during these months. Chronobiologically, the highest mortality rate in the world is also observed at this time.

It is important to understand that our body is primarily regulated by the brain.And no matter how much you eat green vegetables and detox, if the body does not have enough protein and healthy fatty acids (Omega-3, 6, 9), then the brain will have nothing to synthesize neurotransmitters and start recovery. The consequences are quite serious, and the older you are, the more severe it will be manifested by various types of fatigue, sleep and memory disorders. Especially it is necessary to pay attention to people after 35 years. At our institute, special studies of quantum genomics were carried out to create effective drugs for correcting the production of neurotransmitters, including the correction of serotonin production – the drug Triptogen.Interestingly, if you have the first phase of sleep from 12 am to 2 am, then your production of not only melatonin, but also serotonin, is reduced, since these are interrelated processes. Also, in the early stages of exhaustion, a person may not feel tired if his sleep falls between 2 and 5 in the morning. That is, the first and third interrelated phases drop out. But with a long such rhythm, combustion syndrome develops – burnout.

In this syndrome, first of all, the brain and adrenal glands are depleted, but this is already hormonal regulation and we will talk about this next time.

At our institute, we develop highly individual programs to restore sleep, general health, vigor.

What are the parameters of the research?

First, the level of neurotransmitters is measured, special tests are carried out for the most objective assessment of the situation – biochemical, neurophysiological and quantum. It must be said that the needs for different neurotransmitters are different for different people. I see cases where some patients burn the neurotransmitter GABA at a terrible rate, for example, being in a constant state of anxiety due to their professional activities.This includes lawyers, politicians. Deficits are especially severe in those who have to perform a lot in public. We make a correction – and the positive effect is visible immediately.

Sleep is one of the most mysterious and interesting phases of our life. Did you know that Einstein slept 16 hours a day, thereby reaching the creative alpha rhythm. When we sleep, our brains are at different rhythms.

Alpha rhythm is the most creative. Let’s remember the sayings: “the morning is wiser than the evening,” “you need to sleep with each problem,” – they are not accidental.During sleep, our brain, as the most advanced computer, processes all the information and then gives out ready-made solutions. In the case of Einstein, when he woke up, he wrote down his formulas. Mendeleev dreamed of his periodic system. Many poets go to bed and put a notebook and a pen next to them, so that, unexpectedly waking up, they write down the lines of their dreams.

It’s good when you have colorful dreams, for example, a person flies or walks in beautiful places. Some have short, vivid dreams in the early morning hours.Before waking up, our body goes to alpha rhythms. These are the most creative moments.

Another rhythm – beta , this includes thoughts, logic, reflections. But that only accounts for 14% of our brain activity. If we do not get enough sleep, then the efficiency of the brain is reduced. For the sake of fairness, it should be noted that we also reach alpha rhythms in other situations, for example, when a person rides a train with monotonous movement, or when he listens to monotonous speech, or watches a program, listens to music, but at the same time thinks about something else, then the brain finally, he can reach his favorite alpha rhythm, on which he, in fact, creates and recovers.The more you are in a state of alpha rhythm, the more effective and creative your activity will be, the more interesting your life will be. If you want to think about something, you don’t have to sit at the computer, it’s better to take a walk, disconnect, let your brain find the right solution.

There are more theta waves – very deep, a state of deep meditation. This is where medical issues are involved. There are certain types of meditation during which a person enters into theta rhythm.A very intense rhythm, but you can’t stay there for a long time.

To get to theta, you first need to go to alpha rhythms. If you are dreaming, know that your brain is working in a creative way.

There are situations, and this occurs repeatedly, – a person works so hard that he dreams of his work and he wakes up tired. Then you need to change the environment and rest, otherwise you will reduce your performance. And do not think that rest is an empty pastime, it is a reboot of the brain, the way you reboot your computer.The computer writes – to update the data, then it boots and updates the programs. So is our brain, it needs time to shut down.

Does sleep affect antiaging?

Anti-aging and sleep is a particularly interesting topic, I will give a very vivid example. There are cases in history when people were in a coma for 10, 20 years and did not grow old – until the moment they woke up. Scientists believe more and more that we have an aging program in our bodies that is triggered primarily by the brain. People who sleep a lot age much more slowly and are much healthier than those who limit their sleep.This is important to understand.

Someone claims that 5 hours of sleep is enough for him, but for someone 10 hours is not enough, how to explain this?

Those who say they have enough sleep for 5 hours are in a false state of overexcitement. We go to bed late, we do not produce melatonin, because at the same time cortisol is still produced, which is not suppressed by melatonin. We have morning vigor, but it cannot go on all the time. The body cannot fully recover in such a short time.This is a sign of overexcitement. Burnout syndrome will come at some point. Yes, there are situations of stress when we are able to sleep 4-5 hours a day and can be extremely active and efficient. However, these situations are generally compressed. Scientists have shown that we need an average of 7 and a half to 8 hours for effective recovery.

Those who sleep regularly for more than 12 hours and at the same time have difficulty getting up, as a rule, have various deficiencies, primarily of the thyroid gland and, possibly, the adrenal glands.Those with a thyroid gland cannot get up in the morning. Of course, you need to look at everything comprehensively, it can be the thyroid gland, and cortisol, or all together.

There are times when our body needs sleep, for example, after some kind of overload, you are tired and you need to allow yourself to sleep longer. Don’t interfere with your body’s recovery. A healthy sleep will give you health, a good appearance and help to solve weight problems.

Our institute has good experience in the preparation of highly individualized programs.It is for an effective result that people from all over the world turn to us.

We will gladly help you and draw up individual programs for you on the basis of our institute, as well as on the basis of partner clinics and centers. You can find all the information you need on our website:

www.baranovamonaco.com

Information:

Phone: + 377 97 98 04 66

+ 33 (0) 6 80 86 96 38

Address: Monaco Villa Bianca

29 Rue du Portier

98000 Monaco

How sleep affects health | Group of Companies “BUSINESS CAR”

How does the season affect sleep?

– Like various living organisms and plants on Earth – and we are not so different – we adjust to the rhythms of the Sun, and many processes in our body go according to planetary processes, no matter how strange it sounds.

So activity slows down in winter?

– Short daylight hours create a certain difficulty, as the brain is used to rest and recover when the light level decreases. Yes, the active work of the body slows down. Moreover, in winter, the production of both hormones and neurotransmitters of the brain decreases, and of course, this complicates our life. You have heard complaints many times and you yourself have felt a lack of energy in the winter. People often say, “I can’t get up in the morning.”

How to make sure that you are not dependent on these factors and be able to recover as much as possible?

– In the first place, and this applies to all our health, we put sleep and its quality.In my professional experience, people usually don’t know much about this. Many people either try to drink extracts of any plants, or take melatonin everywhere, having heard somewhere that it restores sleep. However, this raises a huge problem.

The normal level of melatonin in the human body is 39, maximum 40 units. Exceeding these values is hazardous to health.

Let me remind you that the sleep period is divided into three fundamentally different phases. The first is the phase of falling asleep, the second is the middle of the night, and the third is the morning rise.And each of the phases is associated with its own problems. To properly start sleep recovery, you need to figure out at which of the three stages you are having difficulties.

Melatonin is a hormone responsible for the first phase of sleep. It is produced in the body from 12 am to 2 am – accordingly, if you go to bed systematically late, you skip this phase. If you are overexcited and unable to sleep, you too are skipping the melatonin production phase.

What other functions does the hormone melatonin perform?

– It has many different functions, including melatonin, which has anti-cancer and antidepressant effects.The most important and insidious mistake is melatonin overdose. I would like to emphasize that the maintenance dose is 0.5 mg, and the corrective dose is 1 mg. If you have special circumstances and you need, say, to fly far, then depending on body weight, you need to take from 2 to 4 mg, but a maximum of 1-3 days.

What do I see in practice? People drink melatonin on the principle that the higher the concentration, the better. And they take it at 4-5 mg for several years. I have patients who have experienced significant sleep and health disorders due to melatonin overdose, which they did not even know about.

Why is an overdose of melatonin dangerous?

– The dream is shortened, becomes very short and very deep and, as the people say, “bad”. Waking up, a person does not understand what is happening to him, he needs some time to come to his senses. Moreover, waking up from such a dream in the middle of the night, a person can no longer fall asleep. Such a short nap is a consequence of an overdose of melatonin.

What happens in case of melatonin overdose?

– Our hormones work on the principle of synergetics and antagonism, that is, they are either “friendly” or “not friendly” with each other.Melatonin is an antagonist of cortisol, the most important hormone of strength and endurance in our body. Melatonin in large quantities begins to suppress it.

In the evening hours we are drawn to sweets, because after 18 hours the production of serotonin starts and there is a lack of it.

The situation is familiar: a person cannot get up in the morning, drinks melatonin – and still sleeps a little. And what does he do? Increases the dose. We ask you to be careful with melatonin. It is best consumed in summer, on long daylight hours.For example, in St. Petersburg, my good friend Professor Vladimir Anisimov, who holds the palm in the discovery of melatonin and work with it, always regularly takes this hormone during the two months of the White Nights – in May and June. This is logical, on white nights the sleep phase completely drops out from 12 am to 2 am. But regardless of the white nights, there is a certain category of people who work very hard. I know those who systematically sleep from 2 to 5-7 in the morning, that is, they completely lose the synthesis of melatonin, which is responsible for antidepressant state, anti-stress, recovery and anti-cancer effects.

How to find the golden mean?

– In order not to be mistaken, it is best to conduct a survey and, if necessary, select the optimal dosage of melatonin. Also, if you are over 40 years old, you have not taken melatonin before and you have difficulty falling asleep or you go to bed late, then taking melatonin 0.5-1 mg before bed for 1-3 months is suitable for you.

Why GABA is a very good amino acid for the brain

GABA is called gamma-aminobutyric acid, which acts as the main suppressive neurotransmitter in the brain.In English, its name looks like Gamma Aminobutyric Acid (GABA).

GABA (gamma-aminobutyric acid) or gamma-aminobutyrate by its nature belongs to amino acids, but performs the function of a neurotransmitter – a substance that transmits an electrical impulse in the body from a nerve cell to a neuron. This is what determines the mechanism of action of GABA, which mainly affects the quality of sleep. But this is not the only valuable property of the amino acid. Thanks to a number of effects, it has found wide application in sports.

What is GABA and what it consists of

If we consider the composition of GABA, it should be noted that glutamate and vitamin B6 are involved in its work. Its main action is soothing. This is because GABA is a neurotransmitter (neurotransmitter). This is the name of a chemical that is found in the brain and ensures the transfer of messages between nerve cells.

A neurotransmitter activates responses to suppress or stimulate an electrical signal that passes through a neuron.Almost all the basic functions of the body depend on this: thoughts, movements, emotions, breathing, sensations, heartbeat, etc.

How GABA acts on the body

The mechanism of action of GABA is to suppress the increased activity of glutamate, which has an exciting effect on neurons. GABA and glutamate are antagonists, that is, substances with the opposite effect:

Glutamate provides attention and concentration, but in excess of it, excessive excitability arises, which leads to anxiety and excitement or even epilepsy.
GABA suppresses overactive activity and maintains a balanced brain.

This is what determines the main effects of taking GABA:

relaxation of a person;
reduction of signs of nervousness;
elimination of mental agitation;
induction of restful sleep;
prevention of depression;
Reducing pain, especially with excessive nervous activity after injury.

We recommend that you study: “How to lower cortisol in order to finally lose weight.”

Thus, GABA promotes better sleep, has nootropic (sedative) and anticonvulsant effects. Acid also improves the absorption of glucose by the brain and improves blood circulation in its tissues, which is important for the health of the organ and increasing intellectual abilities.

Why GABA for athletes and bodybuilders

GABA has the ability to stimulate the anterior pituitary gland – the adenohypophysis.It is she who is responsible for the production of growth hormone growth hormone, which is useful for athletes:

increases the production and slows down the breakdown of protein;
reduces the percentage of adipose tissue in the body;
increases the content of muscle tissue;
acts as an insulin antagonist.

The latter means that growth hormone acts in the opposite direction to insulin. It increases the concentration of glucose in the blood, i.e., like insulin, it is involved in the regulation of metabolism.

The main action of growth hormone is that it forces the body to use fats for energy. Insulin takes glucose for the same purpose. Growth hormone also stimulates regeneration and has a rejuvenating effect. In all this he is helped by gamma-aminobutyric acid.

GABA increases the concentration of growth hormone by 4-6 times. But it should be borne in mind that this is not always enough to increase performance in bodybuilding. Many athletes achieve a more pronounced response due to the administration of growth hormone preparations, which makes it possible to increase its concentration in plasma tens of times.

We recommend to study: “Steroids or sports nutrition: what is the difference”.

Thus, for bodybuilders, the properties of GABA are necessary: 

to increase the level of growth hormone;
Increase fat burning and improve body relief.

Equally important for athletes is the improvement of sleep, which allows them to recover more quickly after serious physical exertion.

Indications for the use of GABA

Taking into account the main properties of GABA, it is recommended to take it according to the following indications:

with general and social anxiety;
panic attacks;
bad mood and depression;
weak stress resistance;
insomnia;
inability to relax and calm down;
chronic pain, including headaches.

You can increase your GABA levels with a ketogenic diet – a low-carb, high-fat diet with a moderate protein content. The amount of carbohydrates is limited to 20-25 g per day. Greens, nuts, berries, vegetables and fatty dairy products are used as carbohydrates.

What GABA contains:

Gaba tea,
tomatoes,
potatoes,
eggplants,
grapefruits,
oranges,
kiwi,
pumpkin, peaches,
carrots,

2726 beets ,

green soybeans.

How to take GABA correctly

According to research, it is optimal to take 3.75 g of GABA per day. The effect of the supplement is felt only at a dose above 2 g. It is better to take GABA after training. The duration of the course is 1-2 months, and after that you can take 2 weeks of rest. It is better to take GABA before bed so that the sports nutrition can maximize its beneficial properties. The effect is manifested already at the end of the first week of admission, and the maximum – after 3 weeks.

To suppress the possible effect of serotonin (an intermediate in the synthesis of melatonin, which suppresses GABA), it is recommended to take GABA together with 5-HTP.

When choosing specific supplements, it is recommended to pay attention to those that contain vitamin B6, since its deficiency impairs the effect of GABA. Examples of effective drugs with GABA (gamma-aminobutyric acid).

Be First GABA Capsules. Take 1-2 capsules daily. Each contains 1200 mg of GABA.

What does the neurotransmitter gaba do: Physiology, GABA – StatPearls – NCBI Bookshelf

Physiology, GABA – StatPearls – NCBI Bookshelf

Introduction

Cellular

Development

Organ Systems Involved

Function

Pathophysiology

Clinical Significance

Continuing Education / Review Questions

References

Physiology, GABA – StatPearls – NCBI Bookshelf

Introduction

Cellular

Development

Organ Systems Involved

Function

Pathophysiology

Clinical Significance

Continuing Education / Review Questions

References

What are the benefits of increased GABA levels in the brain?

Medications to increase GABA

Enhanced thinking and task performance abilities

Stress reduction

Workout recovery and muscle building

GABA, GABA, GABA, what does it actually do in the brain?

3 Amazing Benefits of GABA

What is GABA? – Function, Benefits & Side Effects – Video & Lesson Transcript

GABA as a Supplement

Lesson Summary

Key Terms

Learning Outcome

What is GABA?

Skip to:

What are the role and distribution of GABA?

GABA receptors, agonists and modulators

GABA and the blood-brain barrier

References

Further Reading

Gamma-aminobutyric acid or simply GABA is a chemical compound from the group of amino acids that does not have proteins in its structure.

Useful properties of gamma-aminobutyric acid (GABA)

What role does GABA play in the lives of athletes

GABA

Almighty GABA and the Brain

GABA activity in the brain

Functions of the GABAergic system in the central nervous system.

Factors involved in lowering GABA levels

Gut microbiome: Dysbiosis

Low in zinc, vitamin B6, magnesium, taurine and glutamine

Chronic stress and adrenal fatigue

Poor sleep

Unstable blood sugar

Supplements to increase the level of GABA

Sources:

Gamk (gamma-aminobutyric acid, gaba)

How sleep affects health | Group of Companies “BUSINESS CAR”

Why GABA is a very good amino acid for the brain

What is GABA and what it consists of

How GABA acts on the body

Why GABA for athletes and bodybuilders

Indications for the use of GABA

How to take GABA correctly

Leave a Reply Cancel reply