FREE Γ-Aminobutyric ACID IN BRAIN

Awapara, Jörge; Landua, Alton J.; Fuerst, Robert; Seale, Billie.

doi:10.1016/s0021-9258(19)50926-7

Cited by 320 publications

(32 citation statements)

References 7 publications

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“…Since its discovery in 1950 [ 64 ], GABA has been considered to be the principal inhibitory neurotransmitter in the mammalian brain, playing a crucial role synchronizing the activity of human cortical networks [ 39 ]. About 10% of cells in the brain are GABAergic, and their receptors make up almost half of all receptors in the human brain, being one of the most ubiquitous neurotransmitter systems [ 53 , 65 , 66 ] and participating in a wide range of physiological and behavioral processes, including learning and memory [ 60 , 67 , 68 ].…”

Section: Role Of the Gabaergic System In Cognition And Behaviormentioning

confidence: 99%

GABAergic dysfunction, neural network hyperactivity and memory impairments in human aging and Alzheimer’s disease

Jiménez-Baladó

Eich

2021

Seminars in Cell & Developmental Biology

109

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In this review, we focus on the potential role of the γ-aminobutyric acidergic (GABAergic) system in age-related episodic memory impairments in humans, with a particular focus on Alzheimer’s disease (AD). Well-established animal models have shown that GABA plays a central role in regulating and synchronizing neuronal signaling in the hippocampus, a brain area critical for episodic memory that undergoes early and significant morphologic and functional changes in the course of AD. Neuroimaging research in humans has documented hyperactivity in the hippocampus and losses of resting state functional connectivity in the Default Mode Network, a network that itself prominently includes the hippocampus—presaging episodic memory decline in individuals at-risk for AD. Apolipoprotein ε4, the highest genetic risk factor for AD, is associated with GABAergic dysfunction in animal models, and episodic memory impairments in humans. In combination, these findings suggest that GABA may be the linchpin in a complex system of factors that eventually leads to the principal clinical hallmark of AD: episodic memory loss. Here, we will review the current state of literature supporting this hypothesis. First, we will focus on the molecular and cellular basis of the GABAergic system and its role in memory and cognition. Next, we report the evidence of GABA dysregulations in AD and normal aging, both in animal models and human studies. Finally, we outline a model of GABAergic dysfunction based on the results of functional neuroimaging studies in humans, which have shown hippocampal hyperactivity to episodic memory tasks concurrent with and even preceding AD diagnosis, along with factors that may modulate this association.

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Section: Role Of the Gabaergic System In Cognition And Behaviormentioning

confidence: 99%

GABAergic dysfunction, neural network hyperactivity and memory impairments in human aging and Alzheimer’s disease

Jiménez-Baladó

Eich

2021

Seminars in Cell & Developmental Biology

109

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“…While known as a metabolite in plants and bacteria since the beginning of the 20th century, GABA was not actively studied until its discovery as the major amine present in the brain in 1950 ( 28 , 29 ). The inhibitory function of GABA was first proposed in the late 1950s ( 30 ); however, its role remained controversial for another decade.…”

Section: Historical Perspective and Major Milestones Of Gaba B Researchmentioning

confidence: 99%

Molecular mechanisms of metabotropic GABA _B receptor function

et al. 2021

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Metabotropic γ-aminobutyric acid G protein–coupled receptors (GABAB) represent one of the two main types of inhibitory neurotransmitter receptors in the brain. These receptors act both pre- and postsynaptically by modulating the transmission of neuronal signals and are involved in a range of neurological diseases, from alcohol addiction to epilepsy. A series of recent cryo-EM studies revealed critical details of the activation mechanism of GABAB. Structures are now available for the receptor bound to ligands with different modes of action, including antagonists, agonists, and positive allosteric modulators, and captured in different conformational states from the inactive apo to the fully active state bound to a G protein. These discoveries provide comprehensive insights into the activation of the GABAB receptor, which not only broaden our understanding of its structure, pharmacology, and physiological effects but also will ultimately facilitate the discovery of new therapeutic drugs and neuromodulators.

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“…Because of its importance as a neurotransmitter, GABA’s metabolism has been well characterized in humans and animals [ 39 , 94 , 95 , 96 ]. The liver is considered to be the primary metabolic site for extra-cerebral GABA, and rats display a large capacity for GABA uptake by this organ [ 97 , 98 ].…”

Section: Pharmacokinetics Of Gabamentioning

confidence: 99%

United States Pharmacopeia (USP) Safety Review of Gamma-Aminobutyric Acid (GABA)

et al. 2021

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Gamma-amino butyric acid (GABA) is marketed in the U.S. as a dietary supplement. USP conducted a comprehensive safety evaluation of GABA by assessing clinical studies, adverse event information, and toxicology data. Clinical studies investigated the effect of pure GABA as a dietary supplement or as a natural constituent of fermented milk or soy matrices. Data showed no serious adverse events associated with GABA at intakes up to 18 g/d for 4 days and in longer studies at intakes of 120 mg/d for 12 weeks. Some studies showed that GABA was associated with a transient and moderate drop in blood pressure (<10% change). No studies were available on effects of GABA during pregnancy and lactation, and no case reports or spontaneous adverse events associated with GABA were found. Chronic administration of GABA to rats and dogs at doses up to 1 g/kg/day showed no signs of toxicity. Because some studies showed that GABA was associated with decreases in blood pressure, it is conceivable that concurrent use of GABA with anti-hypertensive medications could increase risk of hypotension. Caution is advised for pregnant and lactating women since GABA can affect neurotransmitters and the endocrine system, i.e., increases in growth hormone and prolactin levels.

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FREE Γ-Aminobutyric ACID IN BRAIN

Cited by 320 publications

References 7 publications

GABAergic dysfunction, neural network hyperactivity and memory impairments in human aging and Alzheimer’s disease

GABAergic dysfunction, neural network hyperactivity and memory impairments in human aging and Alzheimer’s disease

Molecular mechanisms of metabotropic GABA _B receptor function

United States Pharmacopeia (USP) Safety Review of Gamma-Aminobutyric Acid (GABA)

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FREE Γ-Aminobutyric ACID IN BRAIN

Cited by 320 publications

References 7 publications

GABAergic dysfunction, neural network hyperactivity and memory impairments in human aging and Alzheimer’s disease

GABAergic dysfunction, neural network hyperactivity and memory impairments in human aging and Alzheimer’s disease

Molecular mechanisms of metabotropic GABA B receptor function

United States Pharmacopeia (USP) Safety Review of Gamma-Aminobutyric Acid (GABA)

Contact Info

Product

Resources

About

Molecular mechanisms of metabotropic GABA _B receptor function