ArticlePloS one2013
A Transient Upregulation of Glutamine Synthetase in the Dentate Gyrus Is Involved in Epileptogenesis Induced by Amygdala Kindling in the Rat.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 26 citations in OpenAlex.
- Methionine Sulfoximine as a Tool for Studying Temporal Lobe Epilepsy: Initiator, Developer, Attenuator.Neurochemical research · 2025Review
- Astrocytic pathology in Alpers' syndrome.Acta neuropathologica communications · 2023Article
- Inhibition of Glutamate Release, but Not of Glutamine Recycling to Glutamate, Is Involved in Delaying the Onset of Initial Lithium-Pilocarpine-Induced Seizures in Young Rats by a Non-Convulsive MSO Dose.International journal of molecular sciences · 2021Article
- Succinate accumulation induces mitochondrial reactive oxygen species generation and promotes status epilepticus in the kainic acid rat model.Redox biology · 2020Article
- Mode-Dependent Effect of Xenon Inhalation on Kainic Acid-Induced Status Epilepticus in Rats.Frontiers in cellular neuroscience · 2019Article
- Quantitative proteomic analysis of intracerebral hemorrhage in rats with a focus on brain energy metabolism.Brain and behavior · 2018Article
- A Purinergic P2 Receptor Family-Mediated Increase in Thrombospondin-1 Bolsters Synaptic Density and Epileptic Seizure Activity in the Amygdala-Kindling Rat Model.Frontiers in cellular neuroscience · 2018Article
- Linking kindling to increased glutamate release in the dentate gyrus of the hippocampus through the STXBP5/tomosyn-1 gene.Brain and behavior · 2017Article
- Mechanisms of Excessive Extracellular Glutamate Accumulation in Temporal Lobe Epilepsy.Neurochemical research · 2017Review
- Progressive neuronal activation accompanies epileptogenesis caused by hippocampal glutamine synthetase inhibition.Experimental neurology · 2017Article
- Metabolic changes in early poststatus epilepticus measured by MR spectroscopy in rats.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2015Article
- Inhibition of glutamine synthetase in the central nucleus of the amygdala induces anhedonic behavior and recurrent seizures in a rat model of mesial temporal lobe epilepsy.Epilepsy & behavior : E&B · 2015Article
- Inhibition of human glutamine synthetase by L-methionine-S,R-sulfoximine-relevance to the treatment of neurological diseases.Metabolic brain disease · 2014Article
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11 authors at 3 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Reduction of glutamine synthetase (GS) function is closely related to established epilepsy, but little is known regarding its role in epileptogenesis. The present study aimed to elucidate the functional changes of GS in the brain and its involvement in epileptogenesis using the amygdala kindling model of epilepsy induced by daily electrical stimulation of basolateral amygdala in rats. Both expression and activity of GS in the ipsilateral dentate gyrus (DG) were upregulated when kindled seizures progressed to stage 4. A single dose of L-methionine sulfoximine (MSO, in 2 µl), a selective GS inhibitor, was administered into the ipsilateral DG on the third day following the first stage 3 seizure (just before GS was upregulated). It was found that low doses of MSO (5 or 10 µg) significantly and dose-dependently reduced the severity of and susceptibility to evoked seizures, whereas MSO at a high dose (20 µg) aggravated kindled seizures. In animals that seizure acquisition had been successfully suppressed with 10 µg MSO, GS upregulation reoccurred when seizures re-progressed to stage 4 and re-administration of 10 µg MSO consistently reduced the seizures. GLN at a dose of 1.5 µg abolished the alleviative effect of 10 µg MSO and deleterious effect of 20 µg MSO on kindled seizures. Moreover, appropriate artificial microRNA interference (1 and 1.5×10(6) TU/2 µl) of GS expression in the ipsilateral DG also inhibited seizure progression. In addition, a transient increase of GS expression and activity in the cortex was also observed during epileptogenesis evoked by pentylenetetrazole kindling. These results strongly suggest that a transient and region-specific upregulation of GS function occurs when epilepsy develops into a certain stage and eventually promotes the process of epileptogenesis. Inhibition of GS to an adequate degree and at an appropriate timing may be a potential therapeutic approach to interrupting epileptogenesis.
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