ArticleNeuropharmacology2015
Glycine transporter 1 is a target for the treatment of epilepsy.
Article in Neuropharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 49 citations in OpenAlex.
- Solute carrier membrane transporters: emerging targets in CNS disorders.Nature reviews. Drug discovery · 2026Review
- GlyT1 (SLC6A9) inhibition in neurological and psychiatric disorders.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Canine Idiopathic Epilepsy as a Natural Animal Model for Human Epilepsy: A Scoping Review Highlighting Metabolic Perspectives Beyond the Brain.Nutrients · 2026Article
- A model of new-onset refractory status epilepticus (NORSE) using intrahippocampal kainic acid in adolescent mice.Epilepsy research · 2026Article
- Modulation of glycine transporters as a novel therapeutic strategy in neuropsychiatry.Psychopharmacology · 2026Review
- The Metabolic Profile of Plasma During Epileptogenesis in a Rat Model of Lithium-Pilocarpine-Induced Temporal Lobe Epilepsy.Molecular neurobiology · 2025Article
- Editorial to the Special Issue "Glycine-(and D-Serine)-Related Neurotransmission: Promising Therapeutic Targets with Still Unsolved Problems".Biomedicines · 2025Article
- Effect of SSR504734, a Selective Glycine Transporter Type 1 Inhibitor, on Seizure Thresholds, Neurotransmitter Levels, and Inflammatory Markers in Mice.ACS chemical neuroscience · 2025Article
- Classification of Current Experimental Models of Epilepsy.Brain sciences · 2024Review
- Interactions Involving Glycine and Other Amino Acid Neurotransmitters: Focus on Transporter-Mediated Regulation of Release and Glycine-Glutamate Crosstalk.Biomedicines · 2024Review
- Glycine Transporter 1 Inhibitors: Predictions on Their Possible Mechanisms in the Development of Opioid Analgesic Tolerance.Biomedicines · 2024Review
- Interactions between Glycine and Glutamate through Activation of Their Transporters in Hippocampal Nerve Terminals.Biomedicines · 2023Article
- Pentylenetetrazole-Induced Seizures Are Increased after Kindling, Exhibiting Vitamin-Responsive Correlations to the Post-Seizures Behavior, Amino Acids Metabolism and Key Metabolic Regulators in the Rat Brain.International journal of molecular sciences · 2023Article
- Cross-Linking and Functional Analyses for Dimerization of a Cysteine Mutant of Glycine Transporter 1.International journal of molecular sciences · 2022Article
- Metabolomics Provides Novel Insights into Epilepsy Diagnosis and Treatment: A Review.Neurochemical research · 2022Review
- Metabonomic analysis of cerebrospinal fluid in epilepsy.Annals of translational medicine · 2022Article
- Adenosine-AFrontiers in pharmacology · 2022Article
- Impairments of Long-Term Synaptic Plasticity in the Hippocampus of Young Rats during the Latent Phase of the Lithium-Pilocarpine Model of Temporal Lobe Epilepsy.International journal of molecular sciences · 2021Article
- Early Life Febrile Seizures Impair Hippocampal Synaptic Plasticity in Young Rats.International journal of molecular sciences · 2021Article
- Isoliquiritigenin Alleviates Semen Strychni-Induced Neurotoxicity by Restoring the Metabolic Pathway of Neurotransmitters in Rats.Frontiers in pharmacology · 2021Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Glycine is the major inhibitory neurotransmitter in brainstem and spinal cord, whereas in hippocampus glycine exerts dual modulatory roles on strychnine-sensitive glycine receptors and on the strychnine-insensitive glycineB site of the N-methyl-D-aspartate receptor (NMDAR). In hippocampus, the synaptic availability of glycine is largely under control of glycine transporter 1 (GlyT1). Since epilepsy is a disorder of disrupted network homeostasis affecting the equilibrium of various neurotransmitters and neuromodulators, we hypothesized that changes in hippocampal GlyT1 expression and resulting disruption of glycine homeostasis might be implicated in the pathophysiology of epilepsy. Using two different rodent models of temporal lobe epilepsy (TLE)--the intrahippocampal kainic acid model of TLE in mice, and the rat model of tetanic stimulation-induced TLE--we first demonstrated robust overexpression of GlyT1 in the hippocampal formation, suggesting dysfunctional glycine signaling in epilepsy. Overexpression of GlyT1 in the hippocampal formation was corroborated in human TLE samples by quantitative real time PCR. In support of a role of dysfunctional glycine signaling in the pathophysiology of epilepsy, both the genetic deletion of GlyT1 in hippocampus and the GlyT1 inhibitor LY2365109 increased seizure thresholds in mice. Importantly, chronic seizures in the mouse model of TLE were robustly suppressed by systemic administration of the GlyT1 inhibitor LY2365109. We conclude that GlyT1 overexpression in the epileptic brain constitutes a new target for therapeutic intervention, and that GlyT1 inhibitors constitute a new class of antiictogenic drugs. These findings are of translational value since GlyT1 inhibitors are already in clinical development to treat cognitive symptoms in schizophrenia.
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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.