2021
Small loci of astroglial glutamine synthetase deficiency in the postnatal brain cause epileptic seizures and impaired functional connectivity
Farina MG, Sandhu MRS, Parent M, Sanganahalli BG, Derbin M, Dhaher R, Wang H, Zaveri HP, Zhou Y, Danbolt NC, Hyder F, Eid T. Small loci of astroglial glutamine synthetase deficiency in the postnatal brain cause epileptic seizures and impaired functional connectivity. Epilepsia 2021, 62: 2858-2870. PMID: 34536233, PMCID: PMC9006438, DOI: 10.1111/epi.17072.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAstrocytesBrainEpilepsyGlial Fibrillary Acidic ProteinGlutamate-Ammonia LigaseGlutamineHumansMetabolic DiseasesMiceSeizuresConceptsPostnatal brainFunctional connectivityContinuous video-electroencephalographic recordingSpontaneous recurrent seizuresPathogenesis of epilepsyGlutamine synthetase deficiencyVideo-electroencephalographic recordingsSpecific animal modelsEx vivo studySeizure thresholdAdult patientsRecurrent seizuresFocal epilepsyAdeno-associated virusHippocampal formationAnimal modelsFocal mannerEpileptic seizuresGS deficiencySmall lociSynthetase deficiencyEpilepsyGradual returnVivo studiesBrain
2020
Novel aspects of glutamine synthetase in ammonia homeostasis
Zhou Y, Eid T, Hassel B, Danbolt NC. Novel aspects of glutamine synthetase in ammonia homeostasis. Neurochemistry International 2020, 140: 104809. PMID: 32758585, DOI: 10.1016/j.neuint.2020.104809.Peer-Reviewed Original ResearchMeSH KeywordsAmmoniaAnimalsBrainBrain DiseasesGlutamate-Ammonia LigaseGlutamic AcidGlutamineHomeostasisHumansHyperammonemiaLiverConceptsGamma-aminobutyric acidSevere liver diseaseElevated blood ammoniaAmmonia homeostasisInhibitory neurotransmitters glutamateUrea cycleEffects of hyperammonemiaPotassium bufferingNeurological sequelaeBrain edemaLiver diseaseBrain pathophysiologyUrea cycle pathwayBlood ammoniaExtrahepatic tissuesNeurotransmitter glutamateAmmonia clearanceAminobutyric acidComplete urea cycleCycle pathwayTwo-thirdsGlutamine synthetaseRecent studiesHomeostasisBody ammonia
2018
Astrocytes and Glutamine Synthetase in Epileptogenesis
Eid T, Lee T, Patrylo P, Zaveri HP. Astrocytes and Glutamine Synthetase in Epileptogenesis. Journal Of Neuroscience Research 2018, 97: 1345-1362. PMID: 30022509, PMCID: PMC6338538, DOI: 10.1002/jnr.24267.Peer-Reviewed Original ResearchConceptsMesial temporal lobe epilepsyTemporal lobe epilepsyLobe epilepsyAstrocytic glutamine synthetaseRole of astrocytesPotassium channel Kir4.1Important causative factorExcitatory amino acid transporters EAAT1Antiepileptogenic interventionsEpileptogenic insultAntiepileptogenic therapiesEpilepsy developmentChannel Kir4.1Aquaporin-4EpilepsyCausative factorsTransporters EAAT1New targetsSuch interventionsTransporters MCT1DysfunctionAstrocytesMetabolic mechanismsGlutamine synthetaseDownstream effects
2008
Recurrent seizures and brain pathology after inhibition of glutamine synthetase in the hippocampus in rats
Eid T, Ghosh A, Wang Y, Beckström H, Zaveri HP, Lee TS, Lai JC, Malthankar-Phatak GH, de Lanerolle NC. Recurrent seizures and brain pathology after inhibition of glutamine synthetase in the hippocampus in rats. Brain 2008, 131: 2061-2070. PMID: 18669513, PMCID: PMC2724901, DOI: 10.1093/brain/awn133.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsElectroencephalographyEpilepsy, Temporal LobeGlutamate-Ammonia LigaseGlutathioneHippocampusMaleMethionine SulfoximineModels, AnimalRatsRats, Sprague-DawleyRecurrenceConceptsMesial temporal lobe epilepsyMesial temporal sclerosisRecurrent seizuresTemporal sclerosisBrain pathologyIntractable mesial temporal lobe epilepsyTemporal lobe epilepsyGlutamine synthetase deficiencyNovel animal modelContinuous microinfusionHippocampal atrophyLobe epilepsyGlutamate excessNeuropathological featuresExtracellular glutamateHippocampal neuronsAnimal modelsTherapeutic interventionsHippocampusSeizuresSclerosisSynthetase deficiencyMinimal injuryPatientsRats
2004
Loss of glutamine synthetase in the human epileptogenic hippocampus: possible mechanism for raised extracellular glutamate in mesial temporal lobe epilepsy
Eid T, Thomas M, Spencer D, Rundén-Pran E, Lai J, Malthankar G, Kim J, Danbolt N, Ottersen O, de Lanerolle N. Loss of glutamine synthetase in the human epileptogenic hippocampus: possible mechanism for raised extracellular glutamate in mesial temporal lobe epilepsy. The Lancet 2004, 363: 28-37. PMID: 14723991, DOI: 10.1016/s0140-6736(03)15166-5.Peer-Reviewed Original ResearchConceptsMesial temporal lobe epilepsyTemporal lobe epilepsyMTLE hippocampiLobe epilepsyExtracellular glutamateHigh extracellular glutamate concentrationsAnteromedial temporal lobeHuman epileptogenic hippocampusExtracellular glutamate accumulationResolution of seizuresExtracellular glutamate concentrationGlial glutamate transportersMeans of immunohistochemistryEpileptogenic hippocampusSurgical resectionSeizure generationGlutamate homeostasisTemporal lobeAstroglial proliferationEpileptic seizuresGlutamate transportersHippocampusTherapeutic interventionsGlutamate concentrationWestern blot