scholarly journals Gamma-Aminobutyric Acid (GABA) and the Endocannabinoids: Understanding the Risks and Opportunities

2021 ◽  
Author(s):  
Steven P. James ◽  
Dena Bondugji
Keyword(s):  
Cannabinoid Receptors ◽  
Cannabis Sativa ◽  
Strong Relationship ◽  
Therapeutic Benefit ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Inhibitory Neurotransmitter ◽  
Gaba System ◽  
The Many ◽  
Endogenous Cannabinoid

The Gamma-aminobutyric acid (GABA) system is the main inhibitory neurotransmitter system in the central nervous system (CNS) of vertebrates and is involved in critical cellular communication and brain function. The endocannabioid system (ECS) was only recenty discovered and quickly recognized to be abundantly expressed in GABA-rich areas of the brain. The strong relationship between the GABA system and ECS is supported both by studies of the neuraoanatomy of mammalian nervous systems and the chemical messaging between neurons. The ECS is currently known to consist of two endocannabinoids, Anandamide (AEA) and 2-Arachidonyl Glycerol (2-AG), that function as chemical messengers between neurons, at least two cannabinoid receptors (CB1 and CB2), and complex synthetic and degradative metabolic systems. The ECS differs from the GABA system and other neurotransmitter systems in multiple ways including retrograde communication from the activated post-synaptic neuron to the presynaptic cell. Together, this molecular conversation between the ECS and GABA systems regulate the homeostasis and the chemical messaging essential for higher cortical functions such as learning and memory and may play a role in several human pathologies. Phytocannabinoids are synthesized in the plant Cannabis sativa (C. sativa). Within the family of phytocannabinoids at least 100 different cannabinoid molecules or derivatives have been identified and share the properties of binding to the endogenous cannabinoid receptors CB1 and CB2. The well-known psychoactive phytocannabinoid Δ9-tetrahydrocannabinol (THC) and the non-psychoactive cannabidiol (CBD) are just two of the many substances synthesized within C. sativa that act on the body. Although the phytocannabinoids THC and CBD bind to these endogenous receptors in the mammalian CNS, these plant derived molecules have little in common with the endocannabinoids in structure, distribution and metabolism. This overlap in receptor binding is likely coincidental since phytocannabinoids evolved within the plant kingdom and the ECS including the endocannabinoids developed within animals. The GABA and ECS networks communicate through carefully orchestrated activities at localized synaptic level. When phytocannabinoids become available, the receptor affinities for CB1 and CB2 may compete with the naturally occurring endocannabinoid ligands and influence the GABA-ECS communication. In some instances this addition of phytocannabinoids may provide some therapeutic benefit while in other circumstances the presence of these plant derived ligands for the CB1 and CB2 receptors binding site may lead to disruption of important functions within the CNS. The regulatory approval of several THC products for nausea and vomiting and anorexia and CBD for rare pediatric seizure disorders are examples of some of the benefits of phytocannabinoids. Concerns regarding cannabis exposure in utero and in the child and adolescence are shrill warnings of the hazards associated with disrupting the normal maturation of the developing CNS.

GABA System in Depression: Impact on Pathophysiology and Psychopharmacology

2021 ◽  
Vol 28 ◽  
Author(s):  
Alessandra Della Vecchia ◽  
Alessandro Arone ◽  
Armando Piccinni ◽  
Federico Mucci ◽  
Donatella Marazziti
Keyword(s):  
Therapeutic Strategies ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Major Depressive ◽  
Inhibitory Neurotransmitter ◽  
Antidepressant Treatments ◽  
Complex Interactions ◽  
Gaba System ◽  
Clinical Pictures ◽  
Pituitary Adrenal Axis

Background: The pathophysiology of major depressive disorder (MDD), one of the major causes of worldwide disability, is still largely unclear, despite the increasing data reporting evidence of multiple alterations of different systems. Recently, there was a renewed interest in the signalling of gamma aminobutyric acid (GABA) - the main inhibitory neurotransmitter. Objective: The aim of this study was to review and comment on the available literature about the involvement of GABA in MDD, as well as on novel GABAergic compounds possibly useful as antidepressants. Methods: We carried out a narrative review through Pubmed, Google Scholar and Scopus, by using specific keywords. Results : The results, derived from various research tools, strongly support the presence of a deficiency of the GABA system in MDD, which appears to be restored by common antidepressant treatments. More recent publications would indicate the complex interactions between GABA and all the other processes involved in MDD, such as monoamine neurotransmission, hypothalamus-pituitary adrenal axis functioning, neurotrophism, and immune response. Taken together, all these findings seem to further support the complexity of the pathophysiology of MDD, possibly reflecting the heterogeneity of the clinical pictures. Conclusion: Although further data are necessary to support the specificity of GABA deficiency in MDD, the available findings would suggest that novel GABAergic compounds might constitute innovative therapeutic strategies in MDD.

The GABA system and addiction

2018 ◽  
Author(s):  
David J. Nutt ◽  
Liam J. Nestor
Keyword(s):  
Potential Role ◽  
Abuse Liability ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Substance Addiction ◽  
Inhibitory Neurotransmitter ◽  
Gaba System ◽  
Clinical Potential ◽  
The Brain

Research points to the potential role of gamma-aminobutyric acid (GABA) in substance addiction. GABA is the major inhibitory neurotransmitter in the brain. Disturbances in the GABA system may predate substance abuse and addiction, whereby its efficacy to modulate other neurotransmitter systems (e.g. dopamine) strongly implicated in substance addiction behaviours is impaired. There are a number of addictive substances that boost GABA functioning, however, such as alcohol and benzodiazepines. Medications that boost the availability of GABA or mimic its effects at receptors may possess some clinical potential in treating addiction, but also have abuse liability.

scholarly journals The role of γ-aminobutyric acid in aluminum stress tolerance in a woody plant, Liriodendron chinense × tulipifera

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Pengkai Wang ◽  
Yini Dong ◽  
Liming Zhu ◽  
Zhaodong Hao ◽  
LingFeng Hu ◽  
...  
Keyword(s):  
Woody Plant ◽  
Underlying Mechanism ◽  
Absolute Quantification ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Aluminum Stress ◽  
Inhibitory Neurotransmitter ◽  
Al Stress ◽  
Protein Ubiquitination ◽  
Liriodendron Chinense

AbstractThe aluminum (Al) cation Al3+ in acidic soil shows severe rhizotoxicity that inhibits plant growth and development. Most woody plants adapted to acidic soils have evolved specific strategies against Al3+ toxicity, but the underlying mechanism remains elusive. The four-carbon amino acid gamma-aminobutyric acid (GABA) has been well studied in mammals as an inhibitory neurotransmitter; GABA also controls many physiological responses during environmental or biotic stress. The woody plant hybrid Liriodendron (L. chinense × tulipifera) is widely cultivated in China as a horticultural tree and provides high-quality timber; studying its adaptation to high Al stress is important for harnessing its ecological and economic potential. Here, we performed quantitative iTRAQ (isobaric tags for relative and absolute quantification) to study how protein expression is altered in hybrid Liriodendron leaves subjected to Al stress. Hybrid Liriodendron shows differential accumulation of several proteins related to cell wall biosynthesis, sugar and proline metabolism, antioxidant activity, cell autophagy, protein ubiquitination degradation, and anion transport in response to Al damage. We observed that Al stress upregulated glutamate decarboxylase (GAD) and its activity, leading to increased GABA biosynthesis. Additional GABA synergistically increased Al-induced antioxidant enzyme activity to efficiently scavenge ROS, enhanced proline biosynthesis, and upregulated the expression of MATE1/2, which subsequently promoted the efflux of citrate for chelation of Al3+. We also showed similar effects of GABA on enhanced Al3+ tolerance in Arabidopsis. Thus, our findings suggest a function of GABA signaling in enhancing hybrid Liriodendron tolerance to Al stress through promoting organic acid transport and sustaining the cellular redox and osmotic balance.

Molecular Targets of Cannabinoids Associated with Depression

2021 ◽  
Vol 28 ◽  
Author(s):  
Pradeep Paudel ◽  
Samir Ross ◽  
Xing-Cong Li
Keyword(s):  
Gaba Receptor ◽  
Rational Design ◽  
Cannabinoid Receptors ◽  
Molecular Targets ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Binding Modes ◽  
Novel Therapeutic Strategies ◽  
New Treatments ◽  
Synthetic Derivatives

: Novel therapeutic strategies are needed to address depression, a major neurological disorder affecting hundreds of millions of people worldwide. Cannabinoids and their synthetic derivatives have demonstrated numerous neurological activities and may potentially be developed into new treatments for depression. This review highlights cannabinoid (CB) receptors, monoamine oxidase (MAO), N-methyl-D-aspartate (NMDA) receptor, gamma-aminobutyric acid (GABA) receptor, and cholecystokinin (CCK) receptor as key molecular targets of cannabinoids that are associated with depression. The anti-depressant activity of cannabinoids and their binding modes with cannabinoid receptors are discussed, providing insights into rational design and discovery of new cannabinoids or cannabimimetic agents with improved druggable properties.

Plasma concentrations of gamma-aminobutyric acid (GABA) and mood disorders: a blood test for manic depressive disease?

1994 ◽  
Vol 40 (2) ◽  
pp. 296-302 ◽  
Author(s):  
F Petty
Keyword(s):  
Mood Disorders ◽  
Brain Activity ◽  
Plasma Concentrations ◽  
Biological Marker ◽  
Pharmacological Therapy ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Genetic Trait ◽  
Inhibitory Neurotransmitter ◽  
Bipolar Patients

Abstract gamma-Aminobutyric acid (GABA), an inhibitory neurotransmitter that serves about one-third of brain neurons, is involved in the development of depression and in the treatment of depression and mania with pharmacological therapy. Brain activity of GABA may be conveniently measured in plasma, and changes in plasma concentrations of GABA reflect brain GABA activity. Plasma concentrations of GABA are significantly lower than control values in about one-third of patients with major depressive disorder; concentrations are also low in patients with mania and in bipolar patients who are depressed. These low concentrations of GABA appear to persist after recovery from depression and are not increased by treatments that improve depressive symptoms. Follow-up studies suggest that GABA concentrations remain relatively constant over at least 4 years. Additionally, preliminary data suggest that low plasma GABA is a familial marker of mood disorders in a subset of patients. Despite the difficulty of demonstrating that a particular biochemical measure is a true genetic trait marker for vulnerability for development of an illness, the accumulated data suggest that low plasma GABA may represent a biological marker of vulnerability for development of various mood disorders.

THE GAMMA-AMINOBUTYRIC ACID (GABA) SYSTEM IN BRAIN DURING ACUTE AND CHRONIC ETHANOL INTOXICATION

1975 ◽  
Vol 25 (1) ◽  
pp. 43-48 ◽  
Author(s):  
I. A. Sytinsky ◽  
B. M. Guzikov ◽  
M. V. Gomanko ◽  
V. P. Eremin ◽  
N. N. Konovalova
Keyword(s):  
Chronic Ethanol ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Ethanol Intoxication ◽  
Gaba System ◽  
Chronic Ethanol Intoxication

scholarly journals GABA levels in ventral visual cortex decline with age and are associated with neural distinctiveness

2019 ◽  
Author(s):  
Jordan D. Chamberlain ◽  
Holly Gagnon ◽  
Poortata Lalwani ◽  
Kaitlin E. Cassady ◽  
Molly Simmonite ◽  
...  
Keyword(s):  
Older Adults ◽  
Visual Cortex ◽  
Magnetic Resonance ◽  
Aminobutyric Acid ◽  
Resonance Spectroscopy ◽  
Gamma Aminobutyric Acid ◽  
Younger Adults ◽  
Inhibitory Neurotransmitter ◽  
Neural Representations ◽  
Age Related

AbstractAge-related neural dedifferentiation – reduced distinctiveness of neural representations in the aging brain– has been associated with age-related declines in cognitive abilities. But why does neural distinctiveness decline with age? Based on prior work in non-human primates, we hypothesized that the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) declines with age and is associated with neural dedifferentiation. To test this hypothesis, we used magnetic resonance spectroscopy (MRS) to measure GABA and functional MRI (fMRI) to measure neural distinctiveness in the ventral visual cortex in a set of older and younger participants. Relative to younger adults, older adults exhibited lower GABA levels and less distinct activation patterns for faces and houses in the ventral visual cortex. Furthermore, individual differences in GABA within older adults predicted individual differences in neural distinctiveness even after controlling for gray matter volume and age. These results provide novel support for the view that age-related reductions of GABA contribute to age-related reductions in neural distinctiveness (i.e., neural dedifferentiation) in the human ventral visual cortex.Significance StatementNeural representations in the ventral visual cortex are less distinguishable in older compared to younger humans, and this neural dedifferentiation is associated with age-related cognitive deficits. Animal models suggest that reductions in the inhibitory neurotransmitter gamma aminobutyric acid (GABA) may play a role. To investigate this hypothesis, we combined functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS) in a study of the human ventral visual cortex. We observed reduced distinctiveness of neural patterns and reduced GABA levels in older compared to younger adults. Furthermore, older adults with higher GABA levels tended to have more distinctive neural representations. These findings suggest that reduced GABA levels contribute to age-related declines in neural distinctiveness in the human ventral visual cortex.

scholarly journals An Updated Review on Pharmaceutical Properties of Gamma-Aminobutyric Acid

Molecules ◽  
2019 ◽  
Vol 24 (15) ◽  
pp. 2678 ◽  
Author(s):  
Dai-Hung Ngo ◽  
Thanh Sang Vo
Keyword(s):  
Neuronal Development ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Peripheral Tissues ◽  
Inhibitory Neurotransmitter ◽  
Anti Cancer ◽  
The Central Nervous System ◽  
Potential Alternative ◽  
Pharmaceutical Properties ◽  
Anti Inflammation

Gamma-aminobutyric acid (Gaba) is a non-proteinogenic amino acid that is widely present in microorganisms, plants, and vertebrates. So far, Gaba is well known as a main inhibitory neurotransmitter in the central nervous system. Its physiological roles are related to the modulation of synaptic transmission, the promotion of neuronal development and relaxation, and the prevention of sleeplessness and depression. Besides, various pharmaceutical properties of Gaba on non-neuronal peripheral tissues and organs were also reported due to anti-hypertension, anti-diabetes, anti-cancer, antioxidant, anti-inflammation, anti-microbial, anti-allergy, hepato-protection, reno-protection, and intestinal protection. Therefore, Gaba may be considered as potential alternative therapeutics for prevention and treatment of various diseases. Accordingly, this updated review was mainly focused to describe the pharmaceutical properties of Gaba as well as emphasize its important role regarding human health.

Effect of exposure in vitro to ethanol and hypoxia on gamma-aminobutyric acid efflux in the hippocampus of the fetal and adult guinea-pig

1995 ◽  
Vol 7 (5) ◽  
pp. 1339 ◽  
Author(s):  
MC Catlin ◽  
DH Penning ◽  
JF Brien
Keyword(s):  
Guinea Pig ◽  
Hippocampal Slices ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Gaba System ◽  
Direct Exposure ◽  
Interface System ◽  
Near Term ◽  
Co2 Environment

The objective of this study was to determine the effects of acute direct exposure to ethanol, hypoxia or ethanol plus hypoxia on K+-stimulated gamma-aminobutyric acid (GABA) efflux (neuronal release minus uptake) in the hippocampus of the near-term fetal and adult guinea-pig. Transverse hippocampal slices were studied in a static-interface system. Exposure in vitro to ethanol or hypoxia involved 10-min incubation with 50 mM ethanol or 10-min incubation in a 95% N2/5% CO2 environment. GABA was quantitated by HPLC. Ethanol did not alter K+-stimulated GABA efflux; hypoxia augmented K+-stimulated GABA efflux three-fold in the near-term fetus and seven-fold in the adult; concurrent exposure to ethanol did not alter the effect of hypoxia. The data demonstrate that, for acute direct exposure to hypoxia and/or ethanol, only hypoxia increases K+-stimulated GABA efflux, the magnitude of which is dependent on the extent of development of the GABA system.

Synaptic chemistry in single neurons: GABA is identified as an inhibitory neurotransmitter

2005 ◽  
Vol 93 (6) ◽  
pp. 3029-3031 ◽  
Author(s):  
Ronald Harris-Warrick
Keyword(s):  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Single Neurons ◽  
Inhibitory Neurotransmitter ◽  
Historical Significance ◽  
Classic Papers

This essay looks at the historical significance of two APS classic papers that are freely available online: Kravitz EA, Kuffler SW, and Potter DD. Gamma-aminobutyric acid and other blocking compounds in Crustacea. III. Their relative concentrations in separated motor and inhibitory axons. J Neurophysiol 26: 739–751, 1963 ( http://jn.physiology.org/cgi/reprint/26/5/739 ). Otsuka M, Kravitz EA, and Potter DD. Physiological and chemical architecture of a lobster ganglion with particular reference to gamma-aminobutyrate and glutamate. J Neurophysiol 30: 725–752, 1967 ( http://jn.physiology.org/cgi/reprint/30/4/725 ).

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