ArticlePloS one2021
Pharmacological upregulation of GLT-1 alleviates the cognitive impairments in the animal model of temporal lobe epilepsy.
Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- Cerebroprotective potential of ceftriaxone against cadmium chloride-induced cerebral inflammatory changes and oxidative insult.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Ceftriaxone's Multifaceted Neuroprotection in Parkinson's Disease: Preclinical Evidence and Implications for Drug Repurposing.Drug design, development and therapy · 2026Review
- Elucidating the putative role of cannabigerol: a hypothesis-generating review of neuroinflammatory and neuroprotective mechanisms with implications for drug-resistant epilepsy.Frontiers in pharmacology · 2026Review
- Lurasidone ameliorates doxorubicin-induced chemobrain in male Wistar rats: involvement of the hippocampal and prefrontal cortex CREB/BDNF/Glt-1 axis and glutamate homeostasis.Frontiers in pharmacology · 2026Article
- Ceftriaxone suppresses the severity of paclitaxel-induced glutamate-mediated chronic pain in experimental animals.Scientific reports · 2025Article
- Excitatory Amino Acid Transporters as Therapeutic Targets in the Treatment of Neurological Disorders: Their Roles and Therapeutic Prospects.Neurochemical research · 2025Review
- Bromelain Restores Glutamatergic Homeostasis via Regulation of NR2A, GLT-1, EAAC1, and xCT in Arsenic-Induced Cerebral Cortex and Hippocampal Neurotoxicity.F1000Research · 2025Article
- Unraveling the mechanistic interplay of mediators orchestrating the neuroprotective potential of harmine.Pharmacological reports : PR · 2024Review
- The Neurovascular Unit Dysfunction in the Molecular Mechanisms of Epileptogenesis and Targeted Therapy.Neuroscience bulletin · 2024Review
- Riluzole attenuates acute neural injury and reactive gliosis, hippocampal-dependent cognitive impairments and spontaneous recurrent generalized seizures in a rat model of temporal lobe epilepsy.Frontiers in pharmacology · 2024Article
- The m6A reader YTHDC2 promotes the pathophysiology of temporal lobe epilepsy by modulating SLC7A11-dependent glutamate dysregulation in astrocytes.Theranostics · 2024Article
- Depressed glutamate transporter 1 expression in a mouse model of Dravet syndrome.Annals of clinical and translational neurology · 2023Article
- Memantine/Aripiprazole Combination Alleviates Cognitive Dysfunction in Valproic Acid Rat Model of Autism: Hippocampal CREB/BDNF Signaling and Glutamate Homeostasis.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Article
- Functional investigation of SLC1A2 variants associated with epilepsy.Cell death & disease · 2022Article
- Solute carrier transporter disease and developmental and epileptic encephalopathy.Frontiers in neurology · 2022Review
- MicroRNA-mediated regulation of reactive astrocytes in central nervous system diseases.Frontiers in molecular neuroscience · 2022Review
- Converging Mechanisms of Epileptogenesis and Their Insight in Glioblastoma.Frontiers in molecular neuroscience · 2022Review
- Role of glutamate excitotoxicity and glutamate transporter EAAT2 in epilepsy: Opportunities for novel therapeutics development.Biochemical pharmacology · 2021Review
- Ceftriaxone Treatment Weakens Long-Term Synaptic Potentiation in the Hippocampus of Young Rats.International journal of molecular sciences · 2021Article
- Baicalin Rescues Cognitive Dysfunction, Mitigates Neurodegeneration, and Exerts Anti-Epileptic Effects Through Activating TLR4/MYD88/Caspase-3 Pathway in Rats.Drug design, development and therapy · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It is known that hippocampal epileptogenesis is accompanied by hyperexcitability, glutamate-related neuronal dysfunctions and consequently cognitive deficits. However, the neuroprotective role of astrocytic glutamate uptake through the Glutamate Transporter-1 (GLT-1) remains to be unknown in these processes. Therefore, to assess the effect of glutamate uptake, pharmacological upregulation of GLT-1 using ceftriaxone administration (200 mg/kg/day, i.p, 5 days) was utilized in Li-PIL animal models of temporal lobe epilepsy (TLE). Glutamate concentration and glutamine synthetase activity were analyzed using biochemical assays. In addition, GLT-1 gene expression was assessed by RT-qPCR. Finally, cognitive function was studied using Morris water maze (MWM) test and novel object recognition task (NORT). Our results demonstrated that the acute phase of epileptogenesis (first 72 hours after Status Epilepticus) was accompanied by an increase in the hippocampal glutamate and downregulation of GLT-1 mRNA expression compared to controls. Ceftriaxone administration in epileptic animals led to a reduction of glutamate along with elevation of the level of glutamine synthetase activity and GLT-1 expression in the acute phase. In the chronic phase of epileptogenesis (4 weeks after Status Epilepticus), glutamate levels and GLT-1 expression were decreased compared to controls. Ceftriaxone treatment increased the levels of GLT-1 expression. Furthermore, impaired learning and memory ability in the chronic phase of epileptogenesis was rescued by Ceftriaxone administration. This study shows that astrocytic glutamate uptake can profoundly impact the processes of hippocampal epileptogenesis through the reduction of glutamate-induced excitotoxicity and consequently rescuing of cognitive deficits caused by epilepsy.
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