ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
Conditional deletion of the glutamate transporter GLT-1 reveals that astrocytic GLT-1 protects against fatal epilepsy while neuronal GLT-1 contributes significantly to glutamate uptake into synaptosomes.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 178 papers, 1 of them a synthesis that pooled it.
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Who cites it
178 citing papers in PubMed, 1 synthesis or guideline pooled it, 300 citations in OpenAlex.
- EAAT2 as a therapeutic research target in Alzheimer's disease: A systematic review.Frontiers in neuroscience · 2022Pooled it
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- Astrocytes in Genetic Epilepsies: Supporting Actor or Key Player?Journal of neuroscience research · 2026Review
- Functional and Transcriptional Downregulation of Glutamate Transporters (EAAT1 and EAAT2) via DNMT3B Overexpression in Glial Cells.Molecular neurobiology · 2026Article
- Impairment of hippocampal long-term potentiation by soluble amyloid-β oligomers is mediated by glutamate transporter 1 expressed in neurons.Neural regeneration research · 2026Article
- Astroglial kappa opioid receptor-mediated reduction of glutamate exchanger xCT in the prelimbic cortex underlies chronic stress-induced depressive-like behaviors.Molecular psychiatry · 2026Article
- Tau Ablation Rewires Brain Cell Programs in Health and Restores Function in Disease.bioRxiv : the preprint server for biology · 2026Article
- NOTCH3 Mutations in CADASIL: a multicellular perspective on neurodegeneration.Cell communication and signaling : CCS · 2026Review
- Glutamatergic dysfunction of astrocytes in paraventricular nucleus of thalamus contributes to adult anxiety susceptibility in adolescent ethanol exposed mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Astrocytic Igfbp2 Promotes Spontaneous Seizures in a Mouse Model of Mesial Temporal Lobe Epilepsy.Glia · 2026Article
- Disrupted astrocyte-neuron glutamine-glutamate cycling in the medial prefrontal cortex contributes to depression-like behaviors.International journal of biological sciences · 2026Article
- NMDA receptor mediated tonic excitatory currents are elicited by EAAT inhibition on human neocortical pyramidal neurons.Frontiers in synaptic neuroscience · 2026Article
- Neuropharmacological Insights into Glutamate Homeostasis in Post-stroke Depression Regulated by Astrocytes.Current neuropharmacology · 2026Review
- Multi-target neuroprotection of carbon dots derived from Crinis Carbonisatus in multiple acute epilepsy model.Frontiers in molecular biosciences · 2026Article
- TREK-1 and epilepsy: regulating the balance of KBehavioral and brain functions : BBF · 2025Review
- Review
- When the Stars Misfire: Astrocytic Dysfunctions in Major Depressive Disorder.Neurochemical research · 2025Review
- Reactive Astrocytes with Reduced Function of Glutamate Transporters in theACS chemical neuroscience · 2025Article
- Excitatory Amino Acid Transporters as Therapeutic Targets in the Treatment of Neurological Disorders: Their Roles and Therapeutic Prospects.Neurochemical research · 2025Review
- The severity of SLC1A2-associated neurodevelopmental disorders correlates with transporter dysfunction.EBioMedicine · 2025Article
118 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
GLT-1 (EAAT2; slc1a2) is the major glutamate transporter in the brain, and is predominantly expressed in astrocytes, but at lower levels also in excitatory terminals. We generated a conditional GLT-1 knock-out mouse to uncover cell-type-specific functional roles of GLT-1. Inactivation of the GLT-1 gene was achieved in either neurons or astrocytes by expression of synapsin-Cre or inducible human GFAP-CreERT2. Elimination of GLT-1 from astrocytes resulted in loss of ∼80% of GLT-1 protein and of glutamate uptake activity that could be solubilized and reconstituted in liposomes. This loss was accompanied by excess mortality, lower body weight, and seizures suggesting that astrocytic GLT-1 is of major importance. However, there was only a small (15%) reduction that did not reach significance of glutamate uptake into crude forebrain synaptosomes. In contrast, when GLT-1 was deleted in neurons, both the GLT-1 protein and glutamate uptake activity that could be solubilized and reconstituted in liposomes were virtually unaffected. These mice showed normal survival, weight gain, and no seizures. However, the synaptosomal glutamate uptake capacity (Vmax) was reduced significantly (40%). In conclusion, astrocytic GLT-1 performs critical functions required for normal weight gain, resistance to epilepsy, and survival. However, the contribution of astrocytic GLT-1 to glutamate uptake into synaptosomes is less than expected, and the contribution of neuronal GLT-1 to synaptosomal glutamate uptake is greater than expected based on their relative protein expression. These results have important implications for the interpretation of the many previous studies assessing glutamate uptake capacity by measuring synaptosomal uptake.
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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.