ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2019
GAT3 selective substrate l-isoserine upregulates GAT3 expression and increases functional recovery after a focal ischemic stroke in mice.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 31 citations in OpenAlex.
- Article
- Structural basis for selective inhibition of human GABA transporter GAT3.Nature communications · 2026Article
- Clusterin Regulates the Mechanisms of Neuroinflammation and Neuronal Circuit Impairment in Alzheimer's Disease.International journal of molecular sciences · 2025Review
- The Excessive Tonic Inhibition of the Peri-infarct Cortex Depresses Low Gamma Rhythm Power During Poststroke Recovery.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Astrocyte Regulation of Neuronal Function and Survival in Stroke Pathophysiology.Advances in neurobiology · 2024Review
- Aquaporin 4 Depolarization-Enhanced Transferrin Infiltration Leads to Neuronal Ferroptosis after Subarachnoid Hemorrhage in Mice.Oxidative medicine and cellular longevity · 2022Article
- Activation of astroglial CB1R mediates cerebral ischemic tolerance induced by electroacupuncture.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
- More than motor impairment: A spatiotemporal analysis of cognitive impairment and associated neuropathological changes following cortical photothrombotic stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
- The Gliopeptide ODN, a Ligand for the Benzodiazepine Site of GABAThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Targeting GABABrain sciences · 2021Article
- Silk fibroin nanoscaffolds for neural tissue engineering.Journal of materials science. Materials in medicine · 2020Article
- 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
- Discovery of a new class of orthosteric antagonists with nanomolar potency at extrasynaptic GABAScientific reports · 2020Article
- The Delta-Subunit Selective GABAFrontiers in neuroscience · 2019Article
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ischemic stroke triggers an elevation in tonic GABA inhibition that impairs the ability of the brain to form new structural and functional cortical circuits required for recovery. This stroke-induced increase in tonic inhibition is caused by impaired GABA uptake via the glial GABA transporter GAT3, highlighting GAT3 as a novel target in stroke recovery. Using a photothrombotic stroke mouse model, we show that GAT3 protein levels are decreased in peri-infarct tissue from 6 h to 42 days post-stroke. Prior studies have shown that GAT substrates can increase GAT surface expression. Therefore, we aimed to assess whether the GAT3 substrate, L-isoserine, could increase post-stroke functional recovery. L-Isoserine (38 µM or 380 µM) administered directly into the infarct from day 5 to 32 post-stroke, significantly increased motor performance in the grid-walking and cylinder tasks in a concentration-dependent manner, without affecting infarct volumes. Additionally, L-isoserine induced a lasting increase in GAT3 expression in peri-infarct regions accompanied by a small decrease in GFAP expression. This study is the first to show that a GAT3 substrate can increase GAT3 expression and functional recovery after focal ischemic stroke following a delayed long-term treatment. We propose that enhancing GAT3-mediated uptake dampens tonic inhibition and promotes functional recovery after stroke.
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