ArticleEpilepsy research2011
Deletion of the betaine-GABA transporter (BGT1; slc6a12) gene does not affect seizure thresholds of adult mice.
Article in Epilepsy research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
30 citing papers in PubMed, 67 citations in OpenAlex.
- Betaine: A Promising Natural Product for Neurological and Psychiatric Diseases.Current neuropharmacology · 2026Review
- The epigenetic signatures of opioid addiction and physical dependence are prevented by D-cysteine ethyl ester and betaine.Frontiers in pharmacology · 2024Article
- Making the case for prophylactic use of betaine to promote brain health in young (15-24 year old) athletes at risk for concussion.Frontiers in neuroscience · 2023Review
- Reconstitution of GABA, Glycine and Glutamate Transporters.Neurochemical research · 2022Review
- Influence of glutamate and GABA transport on brain excitatory/inhibitory balance.Experimental biology and medicine (Maywood, N.J.) · 2021Review
- Rational approaches for the design of various GABA modulators and their clinical progression.Molecular diversity · 2021Review
- Unearthing of Key Genes Driving the Pathogenesis of Alzheimer's Disease via Bioinformatics.Frontiers in genetics · 2021Article
- Molecular Determinants and Pharmacological Analysis for a Class of Competitive Non-transported Bicyclic Inhibitors of the Betaine/GABA Transporter BGT1.Frontiers in chemistry · 2021Article
- Exploring the molecular determinants for subtype-selectivity of 2-amino-1,4,5,6-tetrahydropyrimidine-5-carboxylic acid analogs as betaine/GABA transporter 1 (BGT1) substrate-inhibitors.Scientific reports · 2020Article
- Pharmacological Characterization of a Betaine/GABA Transporter 1 (BGT1) Inhibitor Displaying an Unusual Biphasic Inhibition Profile and Anti-seizure Effects.Neurochemical research · 2020Article
- The signaling role for chloride in the bidirectional communication between neurons and astrocytes.Neuroscience letters · 2019Review
- HDAC4 gene silencing alleviates epilepsy by inhibition of GABA in a rat model.Neuropsychiatric disease and treatment · 2019Article
- Induction of Osmolyte Pathways in Skeletal Muscle Inflammation: Novel Biomarkers for Myositis.Frontiers in neurology · 2018Article
- Betaine in the Brain: Characterization of Betaine Uptake, its Influence on Other Osmolytes and its Potential Role in Neuroprotection from Osmotic Stress.Neurochemical research · 2017Article
- Attenuated GABAergic Signaling in Intestinal Epithelium Contributes to Pathogenesis of Ulcerative Colitis.Digestive diseases and sciences · 2017Article
- Towards a Better Understanding of GABAergic Remodeling in Alzheimer's Disease.International journal of molecular sciences · 2017Review
- Delineation of the Role of Astroglial GABA Transporters in Seizure Control.Neurochemical research · 2017Review
- The GABA synapse as a target for antiepileptic drugs: a historical overview focused on GABA transporters.Neurochemical research · 2014Review
- EAAT2 (GLT-1; slc1a2) glutamate transporters reconstituted in liposomes argues against heteroexchange being substantially faster than net uptake.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- Pharmacological identification of a guanidine-containing β-alanine analogue with low micromolar potency and selectivity for the betaine/GABA transporter 1 (BGT1).Neurochemical research · 2014Article
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 5 countries.
Funding
Abstract
Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian brain. Once released, it is removed from the extracellular space by cellular uptake catalyzed by GABA transporter proteins. Four GABA transporters (GAT1, GAT2, GAT3 and BGT1) have been identified. Inhibition of the GAT1 by the clinically available anti-epileptic drug tiagabine has been an effective strategy for the treatment of some patients with partial seizures. Recently, the investigational drug EF1502, which inhibits both GAT1 and BGT1, was found to exert an anti-convulsant action synergistic to that of tiagabine, supposedly due to inhibition of BGT1. The present study addresses the role of BGT1 in seizure control and the effect of EF1502 by developing and exploring a new mouse line lacking exons 3-5 of the BGT1 (slc6a12) gene. The deletion of this sequence abolishes the expression of BGT1 mRNA. However, homozygous BGT1-deficient mice have normal development and show seizure susceptibility indistinguishable from that in wild-type mice in a variety of seizure threshold models including: corneal kindling, the minimal clonic and minimal tonic extension seizure threshold tests, the 6Hz seizure threshold test, and the i.v. pentylenetetrazol threshold test. We confirm that BGT1 mRNA is present in the brain, but find that the levels are several hundred times lower than those of GAT1 mRNA; possibly explaining the apparent lack of phenotype. In conclusion, the present results do not support a role for BGT1 in the control of seizure susceptibility and cannot provide a mechanistic understanding of the synergism that has been previously reported with tiagabine and EF1502.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.