How does GABA function as a neurotransmitter. What are the types of GABA receptors. How does GABA affect brain development. What clinical conditions are associated with GABA imbalance.

The Fundamental Role of GABA in the Central Nervous System

Gamma-aminobutyric acid (GABA) is a crucial neurotransmitter in the central nervous system (CNS). Its primary function is to inhibit nerve transmission, effectively reducing neuronal excitability. GABA’s presence is essential for maintaining proper cell membrane stability and overall neurological function.

GABAergic neurons are distributed across various brain regions, including:

• Hippocampus
• Thalamus
• Basal ganglia
• Hypothalamus
• Brainstem

The balance between GABA’s inhibitory action and glutamate’s excitatory effects is vital for optimal CNS functioning. This equilibrium ensures that neural activity is regulated appropriately, preventing excessive excitation that could lead to various neurological disorders.

GABA Synthesis and Metabolism: From Glutamate to Neurotransmitter

Understanding GABA’s synthesis is crucial for appreciating its role in the nervous system. How is GABA produced in the body? GABA is synthesized from glutamate through a process involving glutamate decarboxylase and vitamin B6. This conversion is a key step in the neurotransmitter’s lifecycle.

The synthesis process can be summarized as follows:

1. Glutamate, an excitatory neurotransmitter, serves as the precursor for GABA.
2. Glutamate decarboxylase, with the help of vitamin B6, catalyzes the conversion of glutamate to GABA.
3. Once formed, GABA is released into the post-synaptic terminals of neurons.
4. GABA can be further metabolized to form succinate, which plays a role in the citric acid cycle.

This synthesis pathway highlights the intricate relationship between glutamate and GABA, two neurotransmitters with opposing roles in the nervous system. While glutamate excites neurons, GABA inhibits them, creating a delicate balance necessary for proper neural function.

GABA Receptors: The Gatekeepers of Inhibitory Signaling

GABA receptors are specialized proteins that respond to GABA released in the post-synaptic nerve terminal. These receptors are the primary mediators of inhibitory signaling in the CNS. What are the main types of GABA receptors? GABA receptors are classified into two main categories: GABAa and GABAb.

GABAa Receptors: Fast-Acting Inhibition

GABAa receptors are ligand-gated ion channels responsible for fast synaptic inhibition. Their characteristics include:

• Function as ionotropic receptors
• Upon GABA binding, they open an ion pore allowing chloride to move across the cell membrane
• Chloride influx typically occurs, decreasing the cell’s resting potential and causing an inhibitory effect
• High concentrations in the limbic system and retina

GABAb Receptors: Slow-Acting Inhibition

GABAb receptors are G-protein-coupled receptors that mediate slow synaptic inhibition. Their key features include:

• Activation increases potassium conductance
• Stimulation of adenylyl cyclase, which prevents calcium entry and inhibits presynaptic neurotransmitter release
• Predominantly found in thalamic pathways and the cerebral cortex

The diverse properties of these receptor subtypes allow for a nuanced regulation of neural activity, contributing to the complex functioning of the nervous system.

GABA’s Dual Role in Brain Development: From Excitation to Inhibition

GABA’s role in the developing brain is fascinatingly different from its function in the adult nervous system. During embryonic development, GABA acts as an excitatory neurotransmitter, contrary to its inhibitory role in the mature brain. This shift in function highlights the dynamic nature of neurotransmitter systems during different stages of neural development.

Key aspects of GABA’s role in brain development include:

• GABA is believed to be the first active neurotransmitter in the developing brain
• It plays a crucial role in the proliferation of neuronal progenitor cells
• High levels of GABA in ventricular areas increase proliferation and neural progenitor cell size
• In the subventricular zone, GABA decreases proliferation

This developmental switch in GABA’s function from excitatory to inhibitory is a critical process in neural maturation. Understanding this transition provides insights into normal brain development and may offer clues about neurodevelopmental disorders.

Clinical Implications of GABA Imbalance: From Anxiety to Epilepsy

Alterations in GABA levels or function have been associated with various neurological and psychiatric conditions. How does GABA imbalance manifest in clinical settings? Low levels of GABA have been linked to several disorders, highlighting the neurotransmitter’s importance in maintaining normal brain function.

Psychiatric conditions associated with low GABA levels include:

• Generalized anxiety disorder
• Schizophrenia
• Autism spectrum disorder
• Major depressive disorder

It’s important to note that while GABA concentrations may be altered in these conditions, GABAa receptor agonists are not typically first-line treatments due to their high addiction potential and potentially severe side effects. However, GABA analogs like valproic acid can be used to manage mood instability by enhancing GABA concentrations.

Neurological conditions linked to GABA dysfunction include:

• Seizures and epilepsy
• Movement disorders
• Sleep disturbances

In epilepsy, decreased levels of inhibition in the cerebral cortex can lead to neuronal depolarization and subsequent seizure activity. GABA agonists, such as valproic acid, are commonly used in seizure treatment. Conversely, abrupt withdrawal from GABAergic medications like benzodiazepines can provoke seizures, underscoring the delicate balance of GABA signaling in the brain.

Rare Inherited Disorders of GABA Metabolism: Diagnostic Challenges and Clinical Presentations

While relatively uncommon, inherited disorders of GABA metabolism represent a significant challenge in clinical neurology. These conditions often require a high index of suspicion for accurate diagnosis due to their rarity and sometimes vague presentation. What are the most common inherited GABA metabolism disorders?

The primary inherited GABA metabolism disorders include:

1. GABA-transaminase deficiency
2. Succinic semialdehyde dehydrogenase deficiency (SSADH)
3. Homocarnosinosis

Among these, SSADH is the most frequently encountered neurotransmitter deficiency. Its clinical presentation can be quite variable, encompassing a range of neurological and psychiatric symptoms. In SSADH, GABA cannot be converted to succinic acid, leading to an accumulation of gamma-hydroxybutyrate (GHB).

Key features of SSADH include:

• Vague phenotype with varying neurological manifestations
• Associated psychiatric illness
• Elevated concentrations of GABA and GHB in serum and urine
• Diagnosis through detection of elevated urinary excretion of specific metabolites

These rare disorders highlight the complexity of GABA metabolism and its far-reaching effects on neurological function. They also underscore the importance of considering neurotransmitter imbalances in the differential diagnosis of complex neuropsychiatric presentations.

Therapeutic Approaches Targeting GABA: Balancing Efficacy and Safety

Given GABA’s crucial role in the nervous system, various therapeutic approaches have been developed to modulate GABAergic signaling. These interventions aim to address conditions associated with GABA imbalance while carefully considering potential side effects and addiction risks.

Common therapeutic strategies targeting GABA include:

• GABA receptor agonists (e.g., benzodiazepines for anxiety and insomnia)
• GABA analogs (e.g., gabapentin for neuropathic pain)
• GABA reuptake inhibitors
• Enzymes inhibitors involved in GABA metabolism

While these approaches can be effective, they often come with significant considerations. For instance, benzodiazepines, which act as positive allosteric modulators of GABAa receptors, are highly effective for short-term anxiety relief but carry risks of dependence and cognitive side effects with long-term use.

In epilepsy treatment, various antiepileptic drugs target GABA signaling:

• Valproic acid enhances GABA concentrations
• Tiagabine inhibits GABA reuptake
• Vigabatrin irreversibly inhibits GABA transaminase, increasing GABA levels

These medications have shown efficacy in managing seizures, but their use must be carefully monitored due to potential side effects and drug interactions.

For psychiatric conditions like generalized anxiety disorder or major depression, where GABA dysfunction may play a role, treatment approaches often involve a combination of GABAergic medications and other interventions such as selective serotonin reuptake inhibitors (SSRIs) or cognitive-behavioral therapy.

Researchers are continually exploring novel ways to modulate GABA signaling with improved safety profiles. These efforts include the development of subtype-selective GABA receptor modulators and investigations into the potential of GABA prodrugs or analogues with reduced side effect profiles.

Future Directions in GABA Research: Unraveling Complexities and Exploring New Therapeutic Avenues

As our understanding of GABA’s role in the nervous system continues to evolve, several exciting areas of research are emerging. These investigations promise to shed light on the complexities of GABAergic signaling and potentially lead to new therapeutic strategies.

Key areas of ongoing and future GABA research include:

1. GABA’s role in neurodevelopmental disorders:
   • Investigating the developmental switch from excitatory to inhibitory GABA signaling
   • Exploring potential interventions to correct GABA imbalances in conditions like autism spectrum disorder
2. GABA receptor subtype-specific modulators:
   • Developing drugs that target specific GABA receptor subtypes to improve efficacy and reduce side effects
   • Investigating the potential of these modulators in treating anxiety, epilepsy, and other neurological disorders
3. GABA metabolism and transport:
   • Studying the intricate processes of GABA synthesis, release, and reuptake
   • Identifying new targets for therapeutic intervention in GABA-related disorders
4. GABA’s interaction with other neurotransmitter systems:
   • Exploring the interplay between GABA and glutamate, serotonin, and other neurotransmitters
   • Investigating how these interactions contribute to complex neurological and psychiatric conditions
5. GABA imaging techniques:
   • Developing advanced neuroimaging methods to visualize and quantify GABA levels in the living brain
   • Using these techniques to better understand GABA’s role in various brain functions and disorders

These research directions hold promise for advancing our understanding of GABA’s multifaceted roles in the nervous system. As we uncover more about this crucial neurotransmitter, we may be able to develop more targeted and effective treatments for a wide range of neurological and psychiatric conditions.

Moreover, the exploration of GABA’s functions beyond its role as a neurotransmitter is an emerging area of interest. Recent studies have suggested potential roles for GABA in immune function, metabolism, and even cancer biology. These findings open up new avenues for research and potentially novel therapeutic applications.

In conclusion, GABA’s central role in neural function makes it a critical subject of ongoing neuroscience research. From its basic biochemistry to its complex involvement in brain development and various pathological conditions, GABA continues to fascinate researchers and clinicians alike. As we advance our understanding of this essential neurotransmitter, we move closer to developing more effective and targeted treatments for a wide range of neurological and psychiatric disorders, potentially improving the lives of millions affected by these conditions.

GABA Receptor – StatPearls – NCBI Bookshelf

Mary J. Allen; Sarah Sabir; Sandeep Sharma.

Author Information and Affiliations

Last Update: February 13, 2023.

Introduction

Gamma-aminobutyric acid (GABA) is an amino acid that functions as the primary inhibitory neurotransmitter for the central nervous system (CNS). It functions to reduce neuronal excitability by inhibiting nerve transmission. GABAergic neurons are located when the hippocampus, thalamus, basal ganglia, hypothalamus, and brainstem. The balance between inhibitory neuronal transmission via GABA and excitatory neuronal transmission via glutamate is essential for proper cell membrane stability and neurologic function.

Function

Synthesis

• GABA is formed from glutamate via the addition of glutamate decarboxylase and vitamin B6. GABA can then be used to form succinate, which is involved in the citric acid cycle. Once GABA is formed, is it released into the post-synaptic terminals of neurons.

• Although glutamate is a precursor for GABA, their roles are opposite in the nervous system. Glutamate is considered an excitatory neurotransmitter, while GABA is an inhibitory neurotransmitter. The imbalance of glutamate and GABA can play a role in various pathologies, as discussed in Clinical Significance.[1]

Receptors

• GABA receptors are receptors that respond when GABA is released into the post-synaptic nerve terminal. They are considered the chief inhibitory receptors for the central nervous system. GABA receptors are subdivided into GABAa and GABAb. [2]

• GABAa is classified as a ligand-gated ion channel/inotropic receptor. GABAa is considered in fast synaptic inhibition. Upon the receptor binding to GABA, an ion pore opens to allow chloride to move across the cell membrane. Chloride is a negatively charged ion and will follow into the area of positive charge. Typically, chloride will flow into the intracellular space. The addition of negative charge will decrease the resting potential of the cell, thus causing an inhibitory effect. GABAa receptors are located throughout the central nervous system. However, they have high concentrations in the limbic system and the retina. [2]

• GABAb receptor is a G-couple protein receptor. GABAb receptors are considered slow synaptic inhibitors. After GABA has bound to the receptor, potassium conductance is increased. Adenylyl cyclase is activated, which prevents calcium entry thus inhibits presynaptic release of other neurotransmitters. GABAb locations include the thalamic pathways and cerebral cortex.[3]

Brain Development 

• Within the adult central nervous system, GABA is the primary inhibitory neurotransmitter. However, during embryonic development, GABA acts as an excitatory neurotransmitter. GABA is thought to be the first neurotransmitter active within the developing brain and plays a role in the proliferation of neuronal progenitor cells. High levels of GABA in ventricular areas increased proliferation and neural progenitor cell size; however, in the subventricular zone, GABA decreased proliferation. [4],[5]

Clinical Significance

Various diseases have been associated with low levels of GABA. Many psychiatric illnesses have been linked to low concentrations of GABA. Generalized anxiety is one example. As GABA is an inhibitory neurotransmitter, decreased concentration of it would produce a feeling of anxiousness. It has also been associated with schizophrenia, autism spectrum disorder, and major depressive disorder. It is important to note that although GABA concentrations may be altered in these psychiatric diseases, treatment using GABAa receptor agonists are not first-line therapy, due to high addiction potential and potentially fatal adverse effect. Valproic acid, a GABA analog, can be used for mood instability due to the enhancement of GABA concentrations. [1],[6]

Seizures and epilepsy are associated with low levels of GABA. With decreased levels of inhibition in the cerebral cortex, cells become depolarized, leading to seizure activity. GABA agonists, such as Valproic acid, are used for the treatment of seizures. Abrupt withdrawal from medications such as benzodiazepines, a GABAa positive allosteric modulator, can provoke seizures. Also, GABA antagonists are pro-convulsant. [7]

Inherited disorders of GABA metabolism are rare and therefore require an increase in clinical suspension. The most common diseases are GABA-transaminase deficiency, succinic semialdehyde dehydrogenase deficiency (SSADH), and homocarnosinosis. SSADH is the most common of neurotransmitter deficiencies. It presents with vague phenotype, varying neurological manifestations, and psychiatric illness. GABA is unable to be converted to succinic acid, and gamma-hydroxybutyrate (GHB) accumulates. Elevated concentrations of GABA and GHB are found within serum and urine. Diagnosis can be made with urinary excretion of GABA and increased signaling in the globus pallidus on MRI. Characteristics include expressive language impairment, hypotonia, and seizures. The most common neuropsychiatric problem is sleep disturbance; other issues include inattention, hyperactivity, and obsessive-compulsive disorder (OCD). There is currently no standard treatment for SSADH deficiency. [8]

GABA-transaminase deficiency and homocarnosinosis are much rarer. GABA-transaminase deficiency is an autosomal recessive disorder. Patients may have seizures presenting in the neonatal period; other manifestations include hypotonia, hyperreflexia, severely delayed psychomotor development, and a high-pitched cry. High concentrations of GABA are found in serum and cerebrospinal fluid (CSF). Cerebrospinal fluid is needed for diagnosis. Homocarnosinosis has only been reported in one family. Characteristics include progressive spastic diplegia, intellectual disability, and retinitis pigmentosa. [8]

Other Issues

Pharmacology

GABA Agonist

Drugs that increase the amount of GABA are commonly used as anticonvulsants, sedatives, and anxiolytics. Due to the increase in GABA, CNS depression is a common adverse effect. Some GABA agonist has addiction potential, and use should be monitored closely. [9]

• GABAa receptor agonists: Alcohol (ethanol), barbiturates, and benzodiazepine. Barbiturates include phenobarbital and sodium thiopental. Barbiturates are less frequently used due to the high addiction potential and lack of an antidote. Benzodiazepines have mainly replaced them. Benzodiazepines can treat anxiety, agitation, seizures, and muscle spasms. Only short-term use of benzodiazepine is encouraged. An overdose of benzodiazepines can be fatal due to respiratory depression, especially if concomitant use with alcohol and opioids. Flumazenil is the reversal agent for benzodiazepines. [9]

• GABAb receptor agonists: Baclofen, sodium oxybate (GHB), propofol. GABAb agonists increase CNS depression. Baclofen is typically used as a muscle relaxant to treat spasticity. GHB is approved for the treatment of narcolepsy. Severe CNS depression is common is GHB. Significant respiratory depression and obtundation are commonly seen. Propofol is used for induction and maintenance of general anesthesia. Adverse effects include hypotension, apnea, and involuntary body movements. [9][10][11]

• GABA analogs: Valproic acid, pregabalin, gabapentin. GABA analogs are used as anticonvulsants, sedatives, and anxiolytics. As with other medications that increase GABA, CNS depression is common in this class of drugs. Valproate is prescribed for the treatment of seizures and mood instability. Pregabalin is used for fibromyalgia, diabetic neuropathy, and postherpetic neuralgia. Gabapentin’s approved uses include postherpetic neuralgia and seizures. Off-label uses include diabetic neuropathy and fibromyalgia. [9]

GABA Antagonist

Drugs that bind to but do not increase the amount of GABA are considered antagonists. Examples include picrotoxin or bicuculline methiodide. Both are mainly used for research. GABA antagonists are pro-convulsant and stimulants. [7],[12]

Enhancing Healthcare Team Outcomes

The healthcare team, including physicians, physician assistants, nurse practitioners, nurses, and pharmacists must work together to monitor the usage of GABA receptor agonists. The time should recall that low levels of GABA are associated with seizures and precautions should be taken.

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References

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Wong CG, Bottiglieri T, Snead OC. GABA, gamma-hydroxybutyric acid, and neurological disease. Ann Neurol. 2003;54 Suppl 6:S3-12. [PubMed: 12891648]

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Padgett CL, Slesinger PA. GABAB receptor coupling to G-proteins and ion channels. Adv Pharmacol. 2010;58:123-47. [PubMed: 20655481]

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Schür RR, Draisma LW, Wijnen JP, Boks MP, Koevoets MG, Joëls M, Klomp DW, Kahn RS, Vinkers CH. Brain GABA levels across psychiatric disorders: A systematic literature review and meta-analysis of (1) H-MRS studies. Hum Brain Mapp. 2016 Sep;37(9):3337-52. [PMC free article: PMC6867515] [PubMed: 27145016]

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Chen X, de Haas S, de Kam M, van Gerven J. An Overview of the CNS-Pharmacodynamic Profiles of Nonselective and Selective GABA Agonists. Adv Pharmacol Sci. 2012;2012:134523. [PMC free article: PMC3273701] [PubMed: 22363345]

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Brohan J, Goudra BG. The Role of GABA Receptor Agonists in Anesthesia and Sedation. CNS Drugs. 2017 Oct;31(10):845-856. [PubMed: 29039138]

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Disclosure: Mary Allen declares no relevant financial relationships with ineligible companies.

Disclosure: Sarah Sabir declares no relevant financial relationships with ineligible companies.

Disclosure: Sandeep Sharma declares no relevant financial relationships with ineligible companies.

Physiology, GABA – StatPearls – NCBI Bookshelf

Benjamin E. Jewett; Sandeep Sharma.

Author Information and Affiliations

Last Update: July 25, 2022.

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 Level

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]

Review Questions

• Access free multiple choice questions on this topic.

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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]

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Kondziella D. The Top 5 Neurotransmitters from a Clinical Neurologist’s Perspective. Neurochem Res. 2017 Jun;42(6):1767-1771. [PubMed: 27822666]

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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]

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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]

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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]

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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]

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Wang Q, Ren L, Wan Y, Prud’homme GJ. GABAergic regulation of pancreatic islet cells: Physiology and antidiabetic effects. J Cell Physiol. 2019 Sep;234(9):14432-14444. [PubMed: 30693506]

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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]

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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]

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Hammond JB, Ahmad F. Hepatic encephalopathy and role of antibenzodiazepines. Am J Ther. 1998 Jan;5(1):33-6. [PubMed: 10099035]

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Termsarasab P, Thammongkolchai T, Frucht SJ. Medical treatment of dystonia. J Clin Mov Disord. 2016;3:19. [PMC free article: PMC5168853] [PubMed: 28031858]

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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]

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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]

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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]

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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]

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Jembrek MJ, Vlainic J. GABA Receptors: Pharmacological Potential and Pitfalls. Curr Pharm Des. 2015;21(34):4943-59. [PubMed: 26365137]

Disclosure: Benjamin Jewett declares no relevant financial relationships with ineligible companies.

Disclosure: Sandeep Sharma declares no relevant financial relationships with ineligible companies.

Gamma-aminobutyric acid (GABA)

γ-Aminobutyric acid (abbr. GABA, GABA) is an organic compound, non-proteinogenic amino acid, the most important inhibitory neurotransmitter of the central nervous system (CNS) of humans and other mammals. Aminobutyric acid is a biogenic substance. Contained in the central nervous system and takes part in neurotransmitter and metabolic processes in the brain. Gamma-aminobutyric acid in the body is formed from another amino acid – glutamic acid using the enzyme glutamate decarboxylase.

Gamma-aminobutyric acid ( GABA ) is the main inhibitory neurotransmitter. He is soft, balanced and not very physically coordinated. Its main job is to regulate excitatory signals sent by other neurotransmitters. It allows the muscles and blood vessels to relax and the body to sleep normally. Without his presence, the body would be in danger of dying from convulsions!

Relationship to psychoactive molecules: glutamate, the “big sister” of GABA, is the main excitatory neurotransmitter. Most drugs that interfere with GABA’s work are sedatives, including alcohol, gamma-hydroxybutyric acid (GHB), barbiturates, and benzodiazepines.

GABA . Neurotransmitter is the monopolist of the “industry” of inhibition in the nervous system. He is in a state of eternal struggle for influence with his peppy father Glutamate. The main function is to dampen excitatory signals: GABA convinces neurons (and us, their “owners”) not to respond to the provocations of aggressive neighbors and to remain calm so as not to fall victims of glutamate “intrigues” (for example, a stroke). It is likely that GABA is involved in maintaining a normal sleep cycle and increases glucose uptake. It is possible that it also conducts some signaling pathways in plants – it is not in vain that this is the main amino acid of the tomato apoplast!

So, Gamma-aminobutyric acid (GABA) is the main inhibitory mediator in the human nervous system. But only those of us who have already developed it. And in order to provide us with truly Olympian calm, a motley company of very famous substances sometimes helps her. We will take a closer look at GABA and learn that this molecule is not as simple as it seems at first glance.

Resting neurotransmitter

Gamma-aminobutyric acid (GABA; γ-aminobutyric acid, GABA) is synthesized in the brain from glutamic acid, another neurotransmitter, by its decarboxylation (removal of the carboxyl group from the main chain) (Fig. 1). According to the chemical classification, GABA is an amino acid, but not a habitual one, that is, an α-amino acid used for the synthesis of protein molecules, where the amino group is attached to the first carbon atom in the chain. In GABA, the amino group is linked to the third atom from the carboxyl group (in glutamate, it was the first one before decarboxylation).

Figure 1. Synthesis of GABA. Using the enzyme glutamate decarboxylase (GAD) , another neurotransmitter, GABA, is obtained from the neurotransmitter glutamate.

GABA is synthesized directly in the brain and binds to two types of receptors on the surface of neurons – GABA receptors types A and B. Type A receptors were previously divided into types A and C receptors (found mainly in the retina of the eye), but subsequently were combined in connection with a common action. This type of receptor is ionotropic : when GABA binds to them, an ion channel opens in the nerve cell membrane, and chloride ions rush into the cell, reducing its reactivity. The nerve cell membrane has resting potential . There are fewer charged ions inside the cell than outside, and this creates a charge difference. Outside, superiority is created by chlorine, calcium and sodium, and inside potassium ions and a number of negatively charged organic molecules predominate. In a theoretical sense, the membrane potential has two paths: an increase (called depolarization ) and decrease ( hyperpolarization ) (Fig. 2). At rest, the membrane potential is approximately -70 … -90 mV (millivolts), and when the nervous system is working, a “tug of war” begins between two forces – excitatory cells (depolarizing the membrane) and inhibiting it (hyperpolarizing).

Figure 2. Scheme of the occurrence of action potential on the cell membrane. It is necessary to change the content of ions inside and outside the cell of such strength that the value of the charge on the membrane changes and reaches a certain threshold. If this happens, then the membrane continues to depolarize further, the neuron is excited and transmits a signal to other cells. Overshot (inversion) – the period when the membrane potential is positive. Then the repolarization phase follows, and the membrane charge returns to its previous values.

To understand how this works, two points must be taken into account. The first is that several oppositely directed forces can act on one neuron at the same time: for example, five excitatory and three inhibitory neurons converged on one cell in this part of the nervous system. At the same time, they can affect the dendrite of this neuron and the axon in the presynaptic part. The second point is that a nerve cell experiencing these effects will work according to the “all or nothing” principle. It cannot send a signal and not send it at the same time. All the effects of the signals that came to the cell are summed up, and if the resulting changes in the membrane potential exceed a certain value (called excitation threshold ), then the signal will be transmitted to another cell through the synapse. If the threshold value is not reached, then sorry – try again guys. All this is reminiscent of Krylov’s fable about the swan, cancer and pike: each pulls in its own direction, but it is not very clear what will come of it.

So, the GABA molecule has bound to the ion channel receptor. The ion channel, which has a rather complex structure (Fig. 3), opens and begins to let negatively charged chloride ions into the cell. Under the influence of these ions, the membrane hyperpolarizes, and the cell becomes less susceptible to excitatory signals from other neurons. This is the first and, perhaps, the main function of GABA – inhibition of the activity of nerve cells in the nervous system .

Figure 3. Ionotropic GABA receptor. GABA receptor _A – heteropentamer: consists of 5 protein subunits, which, depending on the homology of amino acid sequences, can belong to eight different families (more often – to α, β, γ; members of the ρ-family are homooligomerized – GABA receptors _A -ρ are obtained, “would former” GABA _C ). This determines the diversity of GABA _A receptors. Scheme of the structure of the receptor. Left: Each of the subunits at the long globular N-terminus extending to the surface of the neuron has a characteristic “cysteine ​​loop” structure and binding sites for GABA and other ligands. This is followed by 4 α-helical transmembrane domains (between the last of them is a large cytoplasmic loop responsible for binding to the cytoskeleton and “internal” modulators) and a short C-terminus. Right: Five subunits form an ion channel, orienting the second transmembrane domain ( orange cylinder ) towards each other. This is the quaternary structure of the receptor. When binding to two GABA molecules, the receptor changes its conformation, opening a pore for anion transport.

Receptors like B are metabotropic , that is, they affect the metabolism in the cell. They also reduce the level of excitation in the cell, but they do it in slower ways, through the G-protein system. Receptors of this type help the cell to reduce sensitivity to excitatory influences through the effect on calcium and potassium channels.

Seizures and anxiety

The structure of the GABAergic system of the brain resembles all the others (Fig. 4). There are a number of structures deep in the brain from where GABA-releasing nerve fibers travel to other parts of the nervous system. Therefore, GABA is an inhibitory neurotransmitter that regulates many processes – from muscle tone to emotional reactions.

Figure 4. GABAergic pathways in the human brain. Accumulations of nerve cells in the depths of the brain send out their processes to different parts of the nervous system in order to reduce the excessive level of excitation.

However, GABA becomes an inhibitory neurotransmitter only in the mature brain. In the developing nervous system, GABAergic neurons can produce an excitatory effect on cells, also changing the membrane permeability to chloride ions [1]. In immature nerve cells, the concentration of chloride ions is higher than in the environment, and stimulation of GABA receptors leads to the release of these anions from the cell and subsequent depolarization of the membrane. Over time, the main excitatory system of the brain matures – glutamate , – and GABA acquires the role of an inhibitory (hyperpolarizing membrane) neurotransmitter.

Brain maturation itself is a complex process that is regulated by many genes at different stages of ontogeny (Fig. 5). Violation of the processes of maturation and migration of neurons leads to various neurological diseases, for example, epilepsy [2]. Epilepsy is one of the most common neurological diseases. With it, brain neurons do not generate nerve impulses as they should – too often and too strongly, which leads to the emergence of a pathological focus of excitation in the brain. It is the existence of such a focus that leads to seizures – the most important and dangerous symptom of epilepsy. Such a “discharge” allows you to temporarily reduce excitation in the nervous system. Mutations in a number of genes lead to the fact that GABAergic interneurons are out of place and cannot fully perform their inhibitory functions. In mouse models and in the study of the human genotype, an association has been established between mutations, impaired migration and maturation of GABAergic neurons, and the development of epilepsy.

Figure 5. Genes responsible for brain maturation are activated at different stages of ontogeny. The embryonic and postnatal periods are separated by a point P0 (birth). The DLX, ARX, DCX, RELN genes are responsible for the growth, maturation and function of inhibitory cells. The DLX (distal-less homeobox) gene family encodes homeodomain-containing transcription factors. Most are expressed during the formation of sensory organs and migration of crest cells and interneurons; regulate gene expression ARX. ARX (aristaless-related homeobox) encodes a homeodomain-containing transcription factor that controls cell differentiation in various organs. In the developing brain, it is essential for the migration of interneurons. DCX (doublecortin) encodes doublecortin (lissencephalin-X), a microtubule-associated protein synthesized in immature neurons during their division (a marker of neurogenesis, including in adults). It is necessary for the correct migration and differentiation of neuroblasts, since it affects the dynamics of cytoskeletal microtubules (stabilizes and groups them). RELN (reelin) – secreted reelin signal glycoprotein gene. With the development of the nervous system, the fibers of the radial glia are oriented in the direction of a greater concentration of reelin, building “paths” for the migration of neurons. This protein is also necessary for the correct construction of the layers of the cortex. RELN is also active in other tissues, even in adults. In the developed brain, reelin is secreted by GABAergic interneurons in the hippocampus and cortex. It probably stimulates the elongation of neuronal processes, affects synaptic plasticity and memory.

Another aspect of the inhibitory action of GABA is its effect on emotional processes, in particular on anxiety. Anxiety is a very broad concept. It contains both completely healthy human reactions to stressful influences (an exam, a dark gateway, a declaration of love), and pathological conditions (anxiety disorders in the medical sense of the word). Based on the provisions of modern psychiatric science, we can say that there are normal anxiety and anxiety as a disease . Anxiety becomes a disease when it interferes with your daily or professional life, blocking you from making any decisions – even the most necessary ones.

The part of the brain that is responsible for emotional reactions is the amygdala – an accumulation of nerve cells in the depths of our head. It is one of the most ancient and important parts of the nervous system in animals. The specialty of the amygdala is negative emotions – we get angry, angry, fearful and anxious through the amygdala. GABA allows the brain to reduce the intensity of these experiences.

Nerve pill

Drugs that are effective in combating anxiety and seizures must bind to the GABA receptor. They are not direct receptor stimulants, i.e. do not bind to the same part of the molecule as GABA. Their role is that they increase the sensitivity of the ion channel to GABA, slightly changing its spatial organization. Such chemicals are called allosteric modulators . Allosteric modulators of GABA receptors include ethanol, benzodiazepines, and barbiturates.

Alcohol is known for its relaxing and anti-anxiety effect. Solutions of ethyl alcohol in various concentrations have long been widely used by the population of the Earth to calm the nerves. Ethanol gives people relaxation by binding to the GABA receptor and facilitating its further interaction with the mediator. It happens that people overestimate their ability to drink alcohol, and this leads to a gradual loss of control over their actions and an increase in lethargy. Alcoholic hyperrelaxation sets in, which, with continued use, can reach an alcoholic coma – the inhibitory effect of alcohol on the central nervous system is so strong. Potentially, alcohol could be used during surgical operations as an anesthetic (previously, in critical situations – for example, at the front – this was done – Rev. ), but the range of concentrations where it turns off pain sensitivity and still does not “turn off” a person completely is too small.

Another class of substances – barbiturates – is now used in neurology for the treatment of epileptic convulsions. All drugs of this class are allosteric modulators, derivatives of barbituric acid – barbital (Fig. 6). Barbital itself was sold by the well-known company Bayer under the trade name “Veronal”. Subsequently, other derivatives of barbituric acid were synthesized: phenobarbital (“Luminal”) and benzobarbital. These drugs, which appeared in the early twentieth century, were the first effective and relatively safe medicine to combat epilepsy. Barbituric acid derivatives have also been used to combat sleep disorders, but in smaller doses.

Figure 6. Barbituric acid molecule.

Another group of drugs that enhance the effect of GABA on cells are benzodiazepines . Like the previous substances, benzodiazepines bind to the GABA type A receptor (Fig. 7). One of the subunits of the ion channel has a special place where the benzodiazepine attaches. All drugs in this class have sedative (sedative), anti-anxiety and anticonvulsant effects. Now psychiatrists and neurologists consider it bad form to treat anxiety and insomnia in patients with long courses of benzodiazepines, and even more so to prescribe them constantly. Dependence is developed to these drugs quite quickly, and withdrawal leads to persistent sleep disturbances and the resumption of anxiety. For these reasons, it is recommended to prescribe benzodiazepines in short courses – for several days.

Note : α1, β2 and γ2 are subunits of the most widely distributed isoform of the GABA _A receptor in the central nervous system. Abbreviations: Cl ^– pore, chloride pore; BDZ, benzodiazepine; ETF, etifoxine; NS, neurosteroid; GABA, gamma-aminobutyric acid (GABA).

The most common combination of subunits in the CNS (about 40% of GABA _A receptors) – two α1, two β2 and one γ2, located around the chloride pore. GABA site (on the surface, junction of α and β) – the place where GABA attaches to the receptor; BDZ site (on the surface, α and γ junction) – benzodiazepine binding site, ETF site (on β) – etifoxine, NS site (in the channel) – neurosteroids. The binding sites for barbiturates and ethanol are presumably located deep in the channel (on the transmembrane domains). In the first case, the β-subunit probably plays the main role, while different subunits, including ρ and δ, interact with ethanol, but their sensitivity differs.

The reason for the dislike of benzodiazepines lies in their side effects, which are quite numerous, and not all of them are taken into account by official structures [4]. First, benzodiazepines, like all GABAergic drugs, are highly addictive. Secondly, benzodiazepines impair a person’s memory. The use of this group of drugs enhances the inhibitory effect of GABA on the cells of the hippocampus – the memory center. This can lead to difficulties in remembering new information, which is observed against the background of the use of benzodiazepines, especially in the elderly.

Physicians currently use antidepressants and other drugs to treat anxiety, such as etifoxine [3]. About this and other groups of drugs used in the complex treatment of not anxiety, but depression, you should look for information in the history of antidepressants . We will give only brief information on antidepressants in the context of GABA and serotonin, the main figure in the annotations of antidepressant drugs. So, a huge number of functions “hang” on serotonin receptors. Through them, a huge number of medicines and drugs realize their effect. And all this could somehow be ignored if it were not for the fact that serotonin is not particularly involved in mood formation at all. The main excitatory neurotransmitter in the human brain is the amino acid glutamate. The main inhibitory is γ-aminobutyric acid (GABA), which is obtained from the same glutamate. Serotonin, dopamine, norepinephrine and other hormones perform auxiliary modulating function.

By the mid-2000s, some mechanisms of the formation of emotions began to become clear. At the same time, from the analysis of biological theories of the development of depression, there is still no single view of the problem (Table 1).

Thus, GABA, despite its narrow “specialty”, is an amazing neurotransmitter. In the developing brain, γ-aminobutyric acid excites nerve cells, while in the developed one, on the contrary, it reduces their activity. She is responsible for a sense of calm, and drugs that activate her receptors bring doctors a lot of reasons for concern. This is how gamma-aminobutyric acid appeared before us – a simple molecule responsible for ensuring that our brains do not “burn out”.

To: Gamma-aminobutyric acid (GABA) and the gut microbiome

Literature

1. Y. Ben-Ari, J.-L. Gaiarsa, R. Tyzio, R. Khazipov. (2007). GABA: A Pioneer Transmitter That Excites Immature Neurons and Generates Primitive Oscillations. Physiological Reviews . 87 , 1215-1284;
2. Bozzi Y., Casarosa S., Caleo M. (2012). Epilepsy as a neurodevelopmental disorder. Front. Psychiatry. 3 , 19;
3. Nuss Ph. (2015). Anxiety disorders and GABA neurotransmission: a disturbance of modulation. Neuropsychiatr. Dis. Treat . 11 , 165–175;
4. Lader M. (2011). Benzodiazepines revisited—will we ever learn? Addiction . 106 , 2086–2109;

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main functions and significance for the body

Content

• 1 Endogenous neurotransmitters
  • 1. 1 Role of endogenous neurotransmitters
  • 1.2 Functions of endogenous neurotransmitters

  90 345 1.3 Importance of endogenous neurotransmitters

  • 1.4 Regulation of body processes
  • 1.5 Involvement of endogenous neurotransmitters in neurotransmission
  • 1.6 Communication between neurons
  • 1.7 Control of physiological processes
  • 1.8 The role of endogenous neurotransmitters in mental health
  • 1.9 The importance of endogenous neurotransmitters for memory and learning
  • 1.10 Related videos:
  • 1.11 Q&A:
    • 90 345 1.11.0.1 What are the functions of endogenous neurotransmitters?
      • 1.11.0.2 What is the importance of endogenous neurotransmitters in the body?
      • 1.11.0.3 Which neurotransmitters are endogenous?
      • 1.11.0.4 What diseases can be associated with an imbalance of endogenous neurotransmitters?
  • 1.12 The influence of endogenous neurotransmitters on comprehensive life
  • 1. 13 Ways to strengthen and improve the work of endogenous neurotransmitters

Endogenous neurotransmitters Mitters are substances synthesized by nerve cells and play an important role in the transmission of nerve impulses in the brain. They affect mood, attention, appetite and other aspects of a person’s mental and physiological activity. Find out how these substances work and what functions they perform.

Neurotransmitters are key elements in the transmission of nerve impulses within the nervous system. They perform important functions by controlling many processes in the body, such as muscle coordination, adaptation to stress, mood and sleep regulation. One type of neurotransmitter is endogenous neurotransmitter, which is produced by the body itself. Unlike exogenous neurotransmitters, which enter the body from outside, endogenous neurotransmitters are of particular importance for the normal functioning of the body.

The main functions of endogenous neurotransmitters include the regulation of neuroplasticity – the ability of nerve cells to change their structure and function in response to certain stimuli. This allows the body to adapt to the external environment and change its behavior according to the circumstances.

In addition, endogenous neurotransmitters play a key role in the regulation of mood and emotions. They affect memory formation processes and cognitive functions such as attention, thinking, and problem solving. Of great importance are endogenous neurotransmitters for learning and remembering information, as well as for controlling anxiety and stress reactions.

In general, endogenous neurotransmitters play an important role in regulating intercellular signals and maintaining body homeostasis. Their deficiency or dysfunction can lead to various pathological conditions such as depression, bipolar disorder, autism, schizophrenia and other neurological diseases.

The role of endogenous neurotransmitters

Endogenous neurotransmitters play an important role in the transmission of signals between neurons and in the regulation of various processes in the body. They act as mediators, providing communication between nerve cells and helping to transfer information from one cell to another.

One of the best known endogenous neurotransmitters is glutamate, which plays a key role in the excitation of the nervous system. It is involved in the formation and maintenance of synaptic connections, helps to transmit signals from a neuron to muscles and other neurons.

Endogenous neurotransmitters such as serotonin, dopamine and norepinephrine play an important role in the regulation of mood and emotional state. A decrease in the level of these neurotransmitters can lead to the development of depression or other mental disorders.

Acetylcholine is not only an endogenous neurotransmitter, but also a hormone. It plays an important role in the process of learning and remembering information, and is also involved in the regulation of sleep and wakefulness.

Oxytocin is known as the hormone of social attachment, but also acts as a neurotransmitter. It is involved in building trusting relationships, increasing feelings of pleasure and reducing stress levels.

Thus, endogenous neurotransmitters play an important role in the normal functioning of the nervous system and the body as a whole. They help regulate various processes, affecting mood, memory, sleep, stress tolerance and many other aspects of our lives.

Endogenous neurotransmitter functions

Neurotransmitters are chemicals that transmit signals between nerve cells in the body. They play an important role in numerous functions by regulating the transmission of information in the nervous system.

Acetylcholine is one of the most important endogenous neurotransmitters. It is involved in the transmission of nerve impulses at neuromuscular junctions, controlling motor functions and the speed of muscle contractions. Acetylcholine is also involved in the regulation of attention, memory, sleep and wakefulness.

Dopamine plays an important role in the control of motor functions, mood, memory, motivation and reward. It also controls the release of the hormone prolactin, which is responsible for regulating lactation in women.

Norepinephrine is responsible for the regulation of emotions, stress response, wakefulness and hunger. This neurotransmitter increases attention and concentration, increases heart rate and blood pressure.

Serotonin plays a key role in the regulation of mood, sleep, appetite, general activity and behaviour. It controls bowel contractions and is involved in the processing of pain signals.

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the central nervous system. GABA is involved in the regulation of anxiety, sleep, muscle tone, and general excitability of the nervous system.

Each of these endogenous neurotransmitters performs specific functions necessary for the normal functioning of the nervous system and the body as a whole. Their imbalance can lead to various disorders such as depression, anxiety, sleep disturbances and other mental and physical problems.

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Importance of endogenous neurotransmitters 9066 6

Endogenous neurotransmitters are important chemicals that play a key role in signaling between nerve cells. They allow you to effectively exchange information within the nervous system and control many processes and functions of the body.

Endogenous neurotransmitters have a variety of functions. They are involved in the regulation of mood, memory, sleep and wakefulness, appetite, functions of organs and systems. They also affect neurogenesis, brain plasticity, and the overall functioning of the nervous system.

Endogenous neurotransmitters include substances such as serotonin, dopamine, acetylcholine, gamma-aminobutyric acid (GABA) and others. Each of them is responsible for certain functions and has its own importance for the proper functioning of the brain and the body as a whole.

Imbalance of endogenous neurotransmitters can lead to various diseases and mental disorders such as depression, schizophrenia, bipolar disorder and others. Therefore, the understanding and study of these substances is important for the development of new methods for the diagnosis, treatment and prevention of such conditions.

In general, endogenous neurotransmitters are an integral part of the nervous system and are essential for maintaining the normal functioning of the body and ensuring mental and physical health.

Regulation of processes in the body

Endogenous neurotransmitters play an important role in the regulation of various processes in the body. They provide signal transmission between nerve cells and are involved in the control of the functions of organs and body systems.

One of the main functions of endogenous neurotransmitters is the regulation of mood and emotions. They are involved in the formation of positive and negative emotional states, as well as in the control of stress and anxiety.

In addition, endogenous neurotransmitters play an important role in the regulation of sleep and wakefulness. They control the transition of the body to a state of sleep and its awakening, and also affect the quality and duration of sleep.

Neurotransmitters are also involved in the regulation of appetite and metabolism. They control hunger and satiety, are involved in food processing and nutrient utilization, and affect the metabolic rate and energy balance of the body.

In addition, endogenous neurotransmitters are involved in the regulation of motor activity and coordination of movements. They control muscle contraction, maintain muscle tone and strength, and are also involved in the formation of motor skills and coordination of movements.

In general, endogenous neurotransmitters play an important role in the regulation of various processes in the body. They provide balance and harmony in the work of organs and systems, ensuring the normal functioning of the body as a whole.

Involvement of endogenous neurotransmitters in neurotransmission

Endogenous neurotransmitters play an important role in neurotransmission – the transmission of signals between neurons in the brain and other parts of the nervous system. Neurotransmitters perform the function of transmitting electrical impulses from one neuron to another, which allows information to move through the nervous system and ensures the normal functioning of the body.

One of the main endogenous neurotransmitters is acetylcholine. It is responsible for the normal function of muscles, including the heart muscle, and is also involved in the process of memory formation and learning. Another important neurotransmitter is gamma-aminobutyric acid (GABA). It is involved in the inhibition of nervous activity, reduces the excitability of neurons and helps to cope with stress and anxiety.

Dopamine is another important endogenous neurotransmitter that plays a role in regulating mood, movement and satisfaction. Serotonin is another important neurotransmitter that is responsible for regulating sleep, appetite, mood, and emotional state. Oxytocin and vasopressin are neurotransmitters responsible for social behavior, social interactions and the formation of bonds between people. They play a key role in building trust and recognition of loved ones.

Communication between neurons

Communication between neurons is the main process of information transfer in the nervous system. It is a complex network of interactions that allows the exchange of signals between individual nerve cells.

The main actors in this process are endogenous neurotransmitters that act as mediators between neurons. They are synthesized in one neuron, stored in synaptic vesicles, and at the moment of activation of the nerve impulse they are released into the synaptic cleft.

The signal from one neuron is transmitted to the next by means of neurotransmitters, which can have an excitatory or inhibitory effect on the receiving neuron. The main significance of endogenous neurotransmitters is the transmission and processing of information in the nervous system, the regulation of body functions and the maintenance of homeostasis.

The process of communication between neurons is a complex and precise system necessary for the normal functioning of the body. Disturbances in this process can lead to various pathologies and diseases, such as depression, bipolar disorder, schizophrenia and other mental disorders.

Control of physiological processes

Endogenous neurotransmitters play an important role in the control of physiological processes in the body. They transmit signals between nerve cells and are key mediators in the nervous system.

One of the main functions of endogenous neurotransmitters is the regulation of muscle contraction. For example, acetylcholine plays an important role in transmitting signals from nerve fibers to muscles, which ensures their controlled contraction. Adrenaline and norepinephrine also affect muscles, increasing physical activity and preparing the body for fight or flight.

In addition, endogenous neurotransmitters regulate important physiological processes such as digestion and excretion. Serotonin, for example, is involved in the regulation of appetite, mood, and sleep. Other neurotransmitters, such as gamma-aminobutyric acid (GABA), regulate the activity of nerve cells by inhibiting excitation.

Endogenous neurotransmitters also play a role in cardiovascular control. They regulate the contraction of the heart and the level of blood pressure. For example, norepinephrine increases heart contraction and increases blood pressure, while acetylcholine lowers blood pressure.

Thus, endogenous neurotransmitters are essential for controlling physiological processes in the body. They regulate the work of muscles, digestion, heart and other systems, ensuring the normal functioning of the body.

The role of endogenous neurotransmitters in mental health

Endogenous neurotransmitters play an important role in maintaining human mental health. They are chemicals that transmit signals between nerve cells in the brain. With a variety of functions, neurotransmitters control mood, emotions, sleep, appetite and other important indicators of the functioning of the body.

One of the main endogenous neurotransmitters is serotonin. It is responsible for the regulation of mood and sleep, and is also involved in learning and memory. Low levels of serotonin are associated with the development of depression, and high levels are associated with aggressiveness and obsessive-compulsive states.

Another important endogenous neurotransmitter is dopamine. It is responsible for pleasure, motivation and physical activity. Low levels of dopamine can cause apathy and depression, while high levels can cause manic states and disruptions in the perception of reality.

Gamma-aminobutyric acid (GABA) is another important neurotransmitter that plays an inhibitory role in the brain. It reduces the excitation of the nervous system and helps to eliminate anxiety and stress. A lack of GABA can lead to anxiety and insomnia, while an excess can cause low blood pressure and drowsiness.

Acetylcholine is another endogenous neurotransmitter that plays an important role in memory, attention and brain function. Abnormal levels of acetylcholine are associated with the development of Alzheimer’s disease and other neurodegenerative diseases.

Thus, endogenous neurotransmitters play a key role in human mental health, controlling mood, emotions, sleep and other important functions. Violations in their level can lead to the development of various mental disorders, so maintaining their balance is an important task for maintaining mental health.

Importance of endogenous neurotransmitters for memory and learning

Endogenous neurotransmitters play an important role in the functioning of memory and learning. They are key mediators of signaling between neurons and allow them to interact and exchange information.

One of the best known endogenous neurotransmitters, acetylcholine, plays an important role in the formation of new memory traces and improvement of cognitive processes. It is actively involved in the formation of short-term memory, as well as in the process of consolidating and storing information in long-term memory.

• Acetylcholine helps to strengthen the connections between neurons, improves attention switching and the ability to memorize.
• Dopamine plays an important role in the formation of motivation and reward, and also increases the effectiveness of learning.
• Serotonin regulates mood and emotional state, which can affect memory and learning processes.

Endogenous neurotransmitters are also associated with learning and brain plasticity. They contribute to the change in synaptic connections and the activation of molecular mechanisms responsible for the formation of new connections between neurons and changes in their structure.

Studies show that changing the concentration of endogenous neurotransmitters can have an effect on memory and learning. For example, certain pharmacological agents that alter the action of neurotransmitters can increase or decrease the ability to remember and learn.

Related videos:

Q&A:

What are the functions of endogenous neurotransmitters?

Endogenous neurotransmitters perform a number of important functions in the body, including signaling between nerve cells, regulation of mood, sleep and appetite, control of memory and cognition, and participation in pain signal processing. They also play a role in regulating body temperature and controlling the cardiovascular system.

What is the importance of endogenous neurotransmitters for the body?

Endogenous neurotransmitters are of great importance for the normal functioning of the body. They allow you to efficiently transmit signals between neurons, ensuring the normal functioning of the nervous system. Without neurotransmitters, it is impossible to perform many important functions of the body, which can lead to serious diseases and disorders.

Which neurotransmitters are endogenous?

Endogenous neurotransmitters include acetylcholine, gamma-aminobutyric acid (GABA), dopamine, serotonin, and norepinephrine. They are synthesized by nerve cells independently and perform key functions in the body.

What diseases can be associated with an imbalance of endogenous neurotransmitters?

Imbalances in endogenous neurotransmitters may be associated with various psychiatric and neurological diseases such as depression, schizophrenia, attention deficit hyperactivity disorder (ADHD), bipolar affective disorder, and others. Dysfunction of the neurotransmitter system can affect mood, emotions, memory, and other cognitive functions.

Influence of endogenous neurotransmitters on comprehensive life functions

Endogenous neurotransmitters play an important role in the regulation of all processes associated with the vital activity of the body. They are mediators of the transmission of nerve impulses and ensure the proper functioning of the nervous system.

Serotonin , one of the main endogenous neurotransmitters, affects mood, appetite, sleep and wakefulness. A lack of serotonin can lead to the development of depression and other mental disorders. An increase in serotonin levels has a beneficial effect on mood and increases the overall activity of the body.

Dopamine is responsible for the feeling of satisfaction and pleasure. It is involved in the regulation of motor activity and contributes to the formation of adaptive reactions. A lack of dopamine can lead to the development of disorders of psychomotor activity and disruption of planned movements. Too much dopamine, on the other hand, can cause motivational problems and addiction to various stimulants.

Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter involved in the regulation of excitatory activity of the nervous system. Its deficiency can cause increased excitability, anxiety, panic. Lack of GABA can lead to sleep disturbances, seizures and is associated with the development of various neurological and psychiatric disorders.

Understanding the role of endogenous neurotransmitters in the regulation of the body’s vital activity allows the development of drugs aimed at correcting their level and balance in the body. This opens up prospects for the emergence of new methods of treating mental and neurological diseases, as well as improving the general condition and quality of human life.

Ways to strengthen and improve endogenous neurotransmitter function

Optimal endogenous neurotransmitter function plays a key role in maintaining the health and normal functioning of the body. There are several ways to strengthen and improve the functioning of these substances to keep the nervous system in good condition.

1. Proper nutrition : A varied and balanced diet is essential for normal synthesis and function of endogenous neurotransmitters. The inclusion of foods rich in amino acids, vitamins and minerals helps to maintain adequate levels of these substances in the body. For example, dietary sources of tryptophan, the amino acid precursor of serotonin, include dark chocolate, bananas, nuts, and seeds.
2. Physical activity : Regular exercise increases the production of endogenous neurotransmitters such as endorphins and serotonin. These substances are natural antidepressants and can improve mood and general well-being.
3. Regular sleep : Sufficient quality sleep is important for the normal functioning of the nervous system. During sleep, the restoration and synthesis of neurotransmitters occurs, which contributes to their optimal work. Sleep disruption can lead to neurotransmitter imbalances and health problems.

In addition, to strengthen and improve the functioning of endogenous neurotransmitters, it is recommended to avoid stressful situations, practice relaxation methods (for example, meditation or yoga), maintain social activity and participate in exciting activities and hobbies. It is important to remember that each body is different, so for the best result, it is recommended to consult a specialist and consult on specific methods to support and improve the work of endogenous neurotransmitters in the appropriate situation.