Featured Publications
Ectopic 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 evidenceSeverityEpilepsy
2019
GATORopathies: The role of amino acid regulatory gene mutations in epilepsy and cortical malformations
Iffland PH, Carson V, Bordey A, Crino PB. GATORopathies: The role of amino acid regulatory gene mutations in epilepsy and cortical malformations. Epilepsia 2019, 60: 2163-2173. PMID: 31625153, PMCID: PMC7155771, DOI: 10.1111/epi.16370.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsCellular amino acid levelsRegulatory gene mutationsActivator RhebAmino acid levelsProtein complexesSingle geneRegulatory proteinsGene mutationsMechanistic targetNPRL3Rapamycin (mTOR) pathwayMTOR activationMTOR pathwayMutationsNPRL2MTOR inhibitionGenesFocal cortical dysplasia type IIaMTORDEPDC5ProteinPivotal rolePathwayRecent studiesNeuronal excitabilitymTOR Hyperactivity Levels Influence the Severity of Epilepsy and Associated Neuropathology in an Experimental Model of Tuberous Sclerosis Complex and Focal Cortical Dysplasia
Nguyen LH, Mahadeo T, Bordey A. mTOR Hyperactivity Levels Influence the Severity of Epilepsy and Associated Neuropathology in an Experimental Model of Tuberous Sclerosis Complex and Focal Cortical Dysplasia. Journal Of Neuroscience 2019, 39: 2762-2773. PMID: 30700531, PMCID: PMC6445990, DOI: 10.1523/jneurosci.2260-18.2019.Peer-Reviewed Original ResearchConceptsFocal cortical dysplasiaTuberous sclerosis complexSeverity of epilepsyRapamycin (mTOR) pathway genesPersonalized medicine strategiesAssociated neuropathologyCortical dysplasiaMouse modelActivity levelsPathogenic variantsEpileptogenic cortical malformationsNeuronal soma sizeMedicine strategiesPatient variantsMechanistic targetSevere epilepsy phenotypePreclinical drug testingHyperactivity levelsDose-dependent mannerMicroglial activationSeizure frequencyRecurrent seizuresCortical malformationsIntractable epilepsyClinical assessment
2016
Switching on mTORC1 induces neurogenesis but not proliferation in neural stem cells of young mice
Mahoney C, Feliciano DM, Bordey A, Hartman NW. Switching on mTORC1 induces neurogenesis but not proliferation in neural stem cells of young mice. Neuroscience Letters 2016, 614: 112-118. PMID: 26812181, DOI: 10.1016/j.neulet.2015.12.042.Peer-Reviewed Original ResearchConceptsNeural stem cellsSubventricular zoneNeonatal subventricular zoneWeek old miceTuberous sclerosis complexStem cellsNewborn neuroblastsYoung miceOld miceProgressive lossYoung adultsRapamycin complex 1Mechanistic targetRecent evidenceProliferative cellsMiceHyperactive mTORC1Terminal differentiationCellsMTORC1 activationProliferationActivationMTORC1NeurogenesisHyperactivity
2015
Hypoxia-inducible factor-1a contributes to dendritic overgrowth in tuberous sclerosis
Zhang L, Feliciano DM, Huang T, Zhang S, Bordey A. Hypoxia-inducible factor-1a contributes to dendritic overgrowth in tuberous sclerosis. Neuroscience Letters 2015, 612: 43-47. PMID: 26655465, PMCID: PMC4728030, DOI: 10.1016/j.neulet.2015.11.038.Peer-Reviewed Original ResearchConceptsHypoxia-inducible factor 1aTuberous sclerosis complexDendritic complexityOlfactory bulb neuronsNeonatal electroporationBulb neuronsTuberous sclerosisTransgenic miceTSC neuronsDendritic patterningNeurological disordersNeuronsCellular alterationsDendritic overgrowthPathological conditionsMRNA levelsRapamycin complex 1Mechanistic targetCognitive disabilitiesData highlightTranscriptional activityVivoFactor 1AOvergrowthLevel contributes