Featured Publications
Expression of 4E-BP1 in juvenile mice alleviates mTOR-induced neuronal dysfunction and epilepsy
Nguyen LH, Xu Y, Mahadeo T, Zhang L, Lin TV, Born HA, Anderson AE, Bordey A. Expression of 4E-BP1 in juvenile mice alleviates mTOR-induced neuronal dysfunction and epilepsy. Brain 2021, 145: 1310-1325. PMID: 34849602, PMCID: PMC9128821, DOI: 10.1093/brain/awab390.Peer-Reviewed Original ResearchConceptsFocal malformationsCortical developmentJuvenile miceCortical spectral activitySpontaneous seizure frequencyIrregular firing patternNovel therapeutic opportunitiesNeuronal cytomegalySeizure frequencyEpilepsy onsetNeuronal abnormalitiesElectrophysiological alterationsIntractable epilepsyNeuronal dysfunctionJuvenile brainMouse modelMTOR pathwayTherapeutic opportunitiesMalformationsFiring patternsEpilepsyAberrant expressionNeurodevelopmental disordersMTOR effectorsMiceEctopic HCN4 expression drives mTOR-dependent epilepsy in mice
Hsieh LS, Wen JH, Nguyen LH, Zhang L, Getz SA, Torres-Reveron J, Wang Y, Spencer DD, Bordey A. Ectopic HCN4 expression drives mTOR-dependent epilepsy in mice. Science Translational Medicine 2020, 12 PMID: 33208499, PMCID: PMC9888000, DOI: 10.1126/scitranslmed.abc1492.Peer-Reviewed Original ResearchConceptsFocal cortical dysplasia type IITuberous sclerosis complexFocal cortical malformationsPyramidal neuronsMouse modelHCN4 expressionCortical pyramidal neuronsOnset of seizuresIntracellular cAMP concentrationSeizure activityCortical malformationsRepetitive firingDiseased neuronsSeizuresAbnormal expressionNeuronsEpilepsyCausative linkSeizure mechanismsCAMP concentrationMechanistic targetHCN4Channel activityPatientsGene therapyConvergent and Divergent Mechanisms of Epileptogenesis in mTORopathies
Nguyen LH, Bordey A. Convergent and Divergent Mechanisms of Epileptogenesis in mTORopathies. Frontiers In Neuroanatomy 2021, 15: 664695. PMID: 33897381, PMCID: PMC8064518, DOI: 10.3389/fnana.2021.664695.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsPI3K-mTOR pathwayCortical developmentGene variantsPotential therapeutic strategyIntractable epilepsyNeuronal placementTherapeutic strategiesAnimal modelsEpilepsyElectrophysiological phenotypeNeurodevelopmental disordersRapamycin complex 1Mechanistic targetEpileptogenesisIndependent mechanismsMTORopathiesGATOR1 complexPersonalized medicineDivergent mechanismsMosaic patternEverolimusMalformationsHyperactivityPathwayVariants
2023
4E-BP1 expression in embryonic postmitotic neurons mitigates mTORC1-induced cortical malformations and behavioral seizure severity but does not prevent epilepsy in mice
Nguyen L, Sharma M, Bordey A. 4E-BP1 expression in embryonic postmitotic neurons mitigates mTORC1-induced cortical malformations and behavioral seizure severity but does not prevent epilepsy in mice. Frontiers In Neuroscience 2023, 17: 1257056. PMID: 37680968, PMCID: PMC10480503, DOI: 10.3389/fnins.2023.1257056.Peer-Reviewed Original ResearchBehavioral seizure severityCortical malformationsSeizure frequencySeizure severityRadial gliaLayer 2/3 pyramidal neuronsCortical layer 2/3 pyramidal neuronsFocal cortical malformationsBehavioral seizuresNeuronal hypertrophyIntractable seizuresPyramidal neuronsSeizure activityRapamycin complex 1 (mTORC1) pathwayEctopic neuronsSeizure preventionMigratory neuronsWhite matterSeizuresNeuronsMalformationsMechanistic targetRecent evidenceSeverityEpilepsyKIF4 Gene Variant’s Disruption of PARP1 Signaling Increases Anxiety and Seizure Susceptibility
Bordey A. KIF4 Gene Variant’s Disruption of PARP1 Signaling Increases Anxiety and Seizure Susceptibility. Epilepsy Currents 2023, 23: 257-258. PMID: 37662464, PMCID: PMC10470092, DOI: 10.1177/15357597231175007.Peer-Reviewed Original ResearchSeizure susceptibilityDevelopmental delayLower seizure thresholdHippocampal pyramidal neuronsSeizure susceptibility phenotypesCommon neurological diseasesPoly (ADP-ribose) polymeraseMild developmental delayKCC2 pathwaySeizure thresholdPyramidal neuronsEpilepsy treatmentMember of kinesinNeurological diseasesNeurological disordersBehavioral testsNeuronal morphologyMutant miceGenetic abnormalitiesIncreases anxietyPotential targetIntellectual disabilityEpilepsySignaling pathwaysSusceptibility phenotype
2022
Current Review in Basic Science: Animal Models of Focal Cortical Dysplasia and Epilepsy
Nguyen LH, Bordey A. Current Review in Basic Science: Animal Models of Focal Cortical Dysplasia and Epilepsy. Epilepsy Currents 2022, 22: 234-240. PMID: 36187145, PMCID: PMC9483763, DOI: 10.1177/15357597221098230.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsFocal cortical dysplasiaFCD type IIAnimal modelsCortical dysplasiaMechanisms of epileptogenesisNumerous animal modelsElectroclinical featuresIntractable epilepsyType IIFCD subtypesFrequent causeCortical developmentPrevalent causeNovel therapeuticsEpilepsyEarly lifeGene mutationsClinical applicationCurrent reviewDysplasiaTechnical considerationsMTORBasic scienceCause
2021
Treating Seizures With Low-Frequency Electrical Stimulation
Bordey A. Treating Seizures With Low-Frequency Electrical Stimulation. Epilepsy Currents 2021, 21: 197-198. PMID: 34867103, PMCID: PMC8609597, DOI: 10.1177/15357597211003559.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMesial temporal lobe epilepsyLow-frequency stimulationTemporal lobe epilepsyLobe epilepsySeizure generationMouse modelElectrical low-frequency stimulationHippocampal low-frequency stimulationFrequency electrical stimulationHippocampal sclerosisSclerotic hippocampusSeizure controlSeizure generalizationGeneralized seizuresSpontaneous seizuresPharmacoresistant epilepsyDaily stimulationGranule cellsElectrical stimulationEpilepsySeizuresCommon formStimulationHippocampusSlice experiments
2014
Selective suppression of excessive GluN2C expression rescues early epilepsy in a tuberous sclerosis murine model
Lozovaya N, Gataullina S, Tsintsadze T, Tsintsadze V, Pallesi-Pocachard E, Minlebaev M, Goriounova NA, Buhler E, Watrin F, Shityakov S, Becker AJ, Bordey A, Milh M, Scavarda D, Bulteau C, Dorfmuller G, Delalande O, Represa A, Cardoso C, Dulac O, Ben-Ari Y, Burnashev N. Selective suppression of excessive GluN2C expression rescues early epilepsy in a tuberous sclerosis murine model. Nature Communications 2014, 5: 4563. PMID: 25081057, PMCID: PMC4143949, DOI: 10.1038/ncomms5563.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsAnticonvulsantsDisease Models, AnimalElectroencephalographyEpilepsyGene Expression RegulationHeterozygoteHumansMaleMiceMice, TransgenicMicrotomyNeocortexPatch-Clamp TechniquesPyrazolesQuinolonesReceptors, N-Methyl-D-AspartateSignal TransductionTissue Culture TechniquesTOR Serine-Threonine KinasesTuberous SclerosisTuberous Sclerosis Complex 1 ProteinTumor Suppressor ProteinsConceptsN-methyl-D-aspartate receptorsTuberous sclerosis complexGluN2C expressionSpiny stellate cellsEarly postnatal lifeGluN2C/DPromising molecular targetBlock seizuresMTOR-dependent mannerSurgical resectionCortical tubersEarly epilepsyUnprovoked seizuresPharmacoresistant epilepsyTSC patientsSeizure generationBrain malformationsFunctional upregulationMurine modelStellate cellsPostnatal lifeRecurrent excitationTumor suppressor geneEpilepsySeizures