ArticleFrontiers in cellular neuroscience2021
The Effect of GLT-1 Upregulation on Extracellular Glutamate Dynamics.
Article in Frontiers in cellular neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 36 citations in OpenAlex.
- Impairment of hippocampal long-term potentiation by soluble amyloid-β oligomers is mediated by glutamate transporter 1 expressed in neurons.Neural regeneration research · 2026Article
- Beta-lactam Antibiotic Cefepime Attenuates Lipopolysaccharide-induced Pain and Depression By Modulating Inflammatory Response and Astroglial Glutamate Transporter in Mice.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026Article
- Glutamate indicators with increased sensitivity and tailored deactivation rates.Nature methods · 2026Article
- From peripheral initiation to central integration: a narrative review of the antihypertensive mechanisms of acupuncture in regulating autonomic nervous system homeostasis.Frontiers in neuroscience · 2026Review
- Ceftriaxone's Multifaceted Neuroprotection in Parkinson's Disease: Preclinical Evidence and Implications for Drug Repurposing.Drug design, development and therapy · 2026Review
- Enriched environment inhibits GLT-1 ubiquitination by downregulating SMURF1 to attenuate ischemic brain injury induced excitotoxicity.Cell & bioscience · 2025Article
- Blueprint of Collapse: Precision Biomarkers, Molecular Cascades, and the Engineered Decline of Fast-Progressing ALS.International journal of molecular sciences · 2025Review
- Positive allosteric modulation of glutamate transporter reduces cocaine-induced locomotion and expression of cocaine conditioned place preference in rats.European journal of pharmacology · 2024Article
- Ceftriaxone and MC-100093 mitigate fentanyl-induced cardiac injury in mice: Preclinical investigation of its underlying molecular mechanisms.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2024Article
- The Purinergic P2X7 Receptor as a Target for Adjunctive Treatment for Drug-Refractory Epilepsy.International journal of molecular sciences · 2024Review
- Current state of neuroprotective therapy using antibiotics in human traumatic brain injury and animal models.BMC neuroscience · 2024Review
- α-Synuclein-carrying astrocytic extracellular vesicles in Parkinson pathogenesis and diagnosis.Translational neurodegeneration · 2023Article
- Glial Glutamate Transporter Modulation Prevents Development of Complete Freund's Adjuvant-Induced Hyperalgesia and Allodynia in Mice.Brain sciences · 2023Article
- Asymmetric dysregulation of glutamate dynamics across the synaptic cleft in a mouse model of Alzheimer's disease.Acta neuropathologica communications · 2023Article
- Bioactive human Alzheimer brain soluble Aβ: pathophysiology and therapeutic opportunities.Molecular psychiatry · 2022Review
- Elevation of Extracellular Glutamate by Blockade of Astrocyte Glutamate Transporters Inhibits Cocaine Reinforcement in Rats via a NMDA-GluN2B Receptor Mechanism.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Ceftriaxone as a Novel Therapeutic Agent for Hyperglutamatergic States: Bridging the Gap Between Preclinical Results and Clinical Translation.Frontiers in neuroscience · 2022Review
- Prophylactic Efficacy of Riluzole against Anxiety- and Depressive-Like Behaviors in Two Rodent Stress Models.Complex psychiatryArticle
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pharmacological upregulation of glutamate transporter-1 (GLT-1), commonly achieved using the beta-lactam antibiotic ceftriaxone, represents a promising therapeutic strategy to accelerate glutamate uptake and prevent excitotoxic damage in neurological conditions. While excitotoxicity is indeed implicated in numerous brain diseases, it is typically restricted to select vulnerable brain regions, particularly in early disease stages. In healthy brain tissue, the speed of glutamate uptake is not constant and rather varies in both an activity- and region-dependent manner. Despite the widespread use of ceftriaxone in disease models, very little is known about how such treatments impact functional measures of glutamate uptake in healthy tissue, and whether GLT-1 upregulation can mask the naturally occurring activity-dependent and regional heterogeneities in uptake. Here, we used two different compounds, ceftriaxone and LDN/OSU-0212320 (LDN), to upregulate GLT-1 in healthy wild-type mice. We then used real-time imaging of the glutamate biosensor iGluSnFR to investigate functional consequences of GLT-1 upregulation on activity- and regional-dependent variations in glutamate uptake capacity. We found that while both ceftriaxone and LDN increased GLT-1 expression in multiple brain regions, they did not prevent activity-dependent slowing of glutamate clearance nor did they speed basal clearance rates, even in areas characterized by slow uptake (e.g., striatum). Unexpectedly, ceftriaxone but not LDN decreased glutamate release in the cortex, suggesting that ceftriaxone may alter release properties independent of its effects on GLT-1 expression. In sum, our data demonstrate the complexities of glutamate uptake by showing that GLT-1 expression does not necessarily translate to accelerated uptake. Furthermore, these data suggest that the mechanisms underlying activity- and regional-dependent differences in glutamate dynamics are independent of GLT-1 expression levels.
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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.