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 effectorsMiceConvulsive seizures from experimental focal cortical dysplasia occur independently of cell misplacement
Hsieh LS, Wen JH, Claycomb K, Huang Y, Harrsch FA, Naegele JR, Hyder F, Buchanan GF, Bordey A. Convulsive seizures from experimental focal cortical dysplasia occur independently of cell misplacement. Nature Communications 2016, 7: 11753. PMID: 27249187, PMCID: PMC4895394, DOI: 10.1038/ncomms11753.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell MovementCognitive DysfunctionDisease Models, AnimalFemaleGene Expression RegulationGenes, ReporterGreen Fluorescent ProteinsHumansMaleMalformations of Cortical DevelopmentMiceNeuronsPrefrontal CortexSeizuresSignal TransductionSirolimusTOR Serine-Threonine KinasesWhite MatterConceptsFocal cortical dysplasiaCortical dysplasiaType II focal cortical dysplasiaWhite matter heterotopiasLayer 2/3 neuronsLife-long treatmentTonic-clonic seizuresNormal survival rateMedial prefrontal cortexLocal malformationsConvulsive seizuresPharmacoresistant epilepsySeizure activitySeizure generationSeizure occurrenceCommon causeCortical developmentMurine modelNeurocognitive impairmentSurvival rateSeizuresRapamycin withdrawalPrefrontal cortexMTOR activityRapamycin treatment
2024
The mTOR pathway genes MTOR, Rheb, Depdc5, Pten, and Tsc1 have convergent and divergent impacts on cortical neuron development and function
Nguyen L, Xu Y, Nair M, Bordey A. The mTOR pathway genes MTOR, Rheb, Depdc5, Pten, and Tsc1 have convergent and divergent impacts on cortical neuron development and function. ELife 2024, 12: rp91010. PMID: 38411613, PMCID: PMC10942629, DOI: 10.7554/elife.91010.Peer-Reviewed Original ResearchConceptsMouse medial prefrontal cortexMedial prefrontal cortexFocal malformations of cortical developmentMalformations of cortical developmentExcitatory synaptic activityExcitatory synaptic transmissionCortical neuron developmentPyramidal neuron morphologyMechanisms of hyperexcitabilityResponse to therapeutic interventionsMTORC1 signalingGene-specific mechanismsPrefrontal cortexFocal malformationsBrain somatic mutationsMTOR complex 1Membrane excitabilityBiallelic inactivationClinical manifestationsGene mutationsNetwork hyperexcitabilitySynaptic transmissionSynaptic activityIntractable epilepsyRepressor gene
2023
In Utero Electroporated Neurons for Medium-Throughput Screening of Compounds Regulating Neuron Morphology
Sokolov A, Aurich M, Bordey A. In Utero Electroporated Neurons for Medium-Throughput Screening of Compounds Regulating Neuron Morphology. ENeuro 2023, 10: eneuro.0160-23.2023. PMID: 37620147, PMCID: PMC10464655, DOI: 10.1523/eneuro.0160-23.2023.Peer-Reviewed Original ResearchConceptsSomatosensory cortexCortical pyramidal neuronsTreatment of epilepsyNeurite overgrowthNeurologic disabilityPyramidal neuronsSoma sizeNovel agentsCircuit alterationsSide effectsMorphologic assessmentMouse neuronsRelated disordersDiseased neuronsMTOR activatorDrug efficacyCandidate therapeuticsNeuronsNeuron morphologyMTOR activityMedium-throughput screeningNeurodevelopmental disordersNeurite lengthMorphologic measurementsDisordersCannabinoid regulation of neurons in the dentate gyrus during epileptogenesis: Role of CB1R‐associated proteins and downstream pathways
Lafourcade C, Sparks F, Bordey A, Wyneken U, Mohammadi M. Cannabinoid regulation of neurons in the dentate gyrus during epileptogenesis: Role of CB1R‐associated proteins and downstream pathways. Epilepsia 2023, 64: 1432-1443. PMID: 36869624, DOI: 10.1111/epi.17569.Peer-Reviewed Original ResearchConceptsTemporal lobe epilepsyDentate gyrusStatus epilepticusProgression of epileptogenesisHippocampal dentate gyrusRole of CB1RCannabinoid regulationHippocampal excitabilityRecurrent seizuresLobe epilepsyRecent findingsEndogenous cannabinoidsBrain injuryClinical trialsEpileptic dischargesNeurologic disordersRetrograde messengerDG circuitryHippocampal formationNeuronal activityTherapeutic interventionsSeizuresEpileptogenesisExcessive excitationCannabinoids
2019
Hypervascularization in mTOR‐dependent focal and global cortical malformations displays differential rapamycin sensitivity
Zhang L, Huang T, Teaw S, Bordey A. Hypervascularization in mTOR‐dependent focal and global cortical malformations displays differential rapamycin sensitivity. Epilepsia 2019, 60: 1255-1265. PMID: 31125447, PMCID: PMC6558978, DOI: 10.1111/epi.15969.Peer-Reviewed Original ResearchConceptsBlood vesselsRapamycin treatmentVessel densityVessel abnormalitiesPostnatal day 14 miceAbsence of seizuresWild-type miceConditional transgenic miceTuberous sclerosis complexTypes of MCDDay 14 miceMCD modelFocal MCDMTOR blockersDysplastic neuronsFunctional outcomeEpilepsy treatmentSomatosensory cortexYoung miceFocal malformationsCortical developmentJuvenile miceTotal vessel lengthAnimal modelsTransgenic mice
2016
Normalizing translation through 4E-BP prevents mTOR-driven cortical mislamination and ameliorates aberrant neuron integration
Lin TV, Hsieh L, Kimura T, Malone TJ, Bordey A. Normalizing translation through 4E-BP prevents mTOR-driven cortical mislamination and ameliorates aberrant neuron integration. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: 11330-11335. PMID: 27647922, PMCID: PMC5056085, DOI: 10.1073/pnas.1605740113.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsCarrier ProteinsCell Cycle ProteinsDendritic SpinesEukaryotic Initiation FactorsExcitatory Postsynaptic PotentialsGene Knockdown TechniquesGreen Fluorescent ProteinsMatrix Attachment Region Binding ProteinsMechanistic Target of Rapamycin Complex 1MiceNeurogliaNeuronsPhosphoproteinsProtein BiosynthesisRas Homolog Enriched in Brain ProteinRNA CapsRNA, Small InterferingSignal TransductionTOR Serine-Threonine KinasesTranscription FactorsConceptsBrain cytoarchitectureUpper layer cortical neuronsHyperactive mammalian targetDendritic hypertrophyCortical neuronsCap-dependent translationEctopic placementRadial gliaMammalian targetLate corticogenesisTranslational repressor eukaryotic initiation factor 4EEukaryotic initiation factor 4ENeurodevelopmental disordersProtein 1Rapamycin complex 1Molecular hallmarksInitiation factor 4EMechanisms downstreamCytoarchitectureMolecular identityMisplacementActive mutantHypertrophyGliaOveractivation
2015
The multifaceted subventricular zone astrocyte: From a metabolic and pro-neurogenic role to acting as a neural stem cell
Platel JC, Bordey A. The multifaceted subventricular zone astrocyte: From a metabolic and pro-neurogenic role to acting as a neural stem cell. Neuroscience 2015, 323: 20-28. PMID: 26546469, PMCID: PMC4821790, DOI: 10.1016/j.neuroscience.2015.10.053.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsVentricular-subventricular zoneNeural progenitor cellsPro-neurogenic roleHippocampal dentate gyrusNeural stem cellsSubgranular zoneNewborn neuronsNeurogenic propertiesDentate gyrusNew neuronsLateral ventricleAdult brainMature astrocytesTranscription factor expressionNeurogenic fateNeurophysiological characteristicsFactor expressionAstrocytesBlood vesselsProgenitor cellsMetabolic couplingSurvival cuesNeuronsStem cellsCellsNoncanonical Sites of Adult Neurogenesis in the Mammalian Brain
Feliciano DM, Bordey A, Bonfanti L. Noncanonical Sites of Adult Neurogenesis in the Mammalian Brain. Cold Spring Harbor Perspectives In Biology 2015, 7: a018846. PMID: 26384869, PMCID: PMC4588058, DOI: 10.1101/cshperspect.a018846.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements
2013
Rheb Activation in Subventricular Zone Progenitors Leads to Heterotopia, Ectopic Neuronal Differentiation, and Rapamycin-Sensitive Olfactory Micronodules and Dendrite Hypertrophy of Newborn Neurons
Lafourcade CA, Lin TV, Feliciano DM, Zhang L, Hsieh LS, Bordey A. Rheb Activation in Subventricular Zone Progenitors Leads to Heterotopia, Ectopic Neuronal Differentiation, and Rapamycin-Sensitive Olfactory Micronodules and Dendrite Hypertrophy of Newborn Neurons. Journal Of Neuroscience 2013, 33: 2419-2431. PMID: 23392671, PMCID: PMC3711634, DOI: 10.1523/jneurosci.1840-12.2013.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornCell DifferentiationCell EnlargementCell Line, TumorCell MovementCerebral VentriclesDendritesElectroporationFemaleHypertrophyMaleMiceMonomeric GTP-Binding ProteinsNeural Stem CellsNeurogenesisNeuronsNeuropeptidesOlfactory BulbRas Homolog Enriched in Brain ProteinSirolimusStem CellsTOR Serine-Threonine KinasesConceptsNeural progenitor cellsWild-type miceOlfactory bulbMTOR activitySynaptic inputsEctopic neuronal differentiationSubventricular zone neural progenitor cellsActive ras homologNeuronal differentiationGABAergic synaptic inputsTsc1 mutant miceSubventricular zone progenitorsDendritic complexityNewborn neuronsTuberous sclerosisOlig2 cellsHyperactive mTORHeterozygote miceCircuit formationAction potentialsNeuronal morphologyNewborn cellsMutant miceEctopic cellsMammalian targetHypoxia-inducible factor 1a is a Tsc1-regulated survival factor in newborn neurons in tuberous sclerosis complex
Feliciano DM, Zhang S, Quon JL, Bordey A. Hypoxia-inducible factor 1a is a Tsc1-regulated survival factor in newborn neurons in tuberous sclerosis complex. Human Molecular Genetics 2013, 22: 1725-1734. PMID: 23349360, PMCID: PMC3613161, DOI: 10.1093/hmg/ddt018.Peer-Reviewed Original ResearchConceptsHypoxia-inducible factor 1aTuberous sclerosis complexShort hairpin RNANewborn neuronsFactor 1ASubventricular zoneSVZ stem cellsNewborn neuron survivalNeurogenic subventricular zoneSingle-cell electroporationTranscriptional activityShRNA expressionHairpin RNAMammalian targetMolecular determinantsNovel microenvironmentNeuron deathNeuron survivalOlfactory lesionsNeonatal miceBrain lesionsStem cellsMouse modelNeuron productionSurvival advantage
2012
NKCC1 Knockdown Decreases Neuron Production through GABAA-Regulated Neural Progenitor Proliferation and Delays Dendrite Development
Young SZ, Taylor MM, Wu S, Ikeda-Matsuo Y, Kubera C, Bordey A. NKCC1 Knockdown Decreases Neuron Production through GABAA-Regulated Neural Progenitor Proliferation and Delays Dendrite Development. Journal Of Neuroscience 2012, 32: 13630-13638. PMID: 23015452, PMCID: PMC3478384, DOI: 10.1523/jneurosci.2864-12.2012.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAnalysis of VarianceAnimalsAnimals, NewbornCalciumCell CountCell DifferentiationCell ProliferationCells, CulturedCerebral VentriclesDendritesEgtazic AcidElectroporationFemaleGABA ModulatorsGABA-A Receptor AgonistsGreen Fluorescent ProteinsIn Vitro TechniquesKi-67 AntigenLuminescent ProteinsMaleMiceMuscimolNeural Stem CellsNeuronsOlfactory BulbPatch-Clamp TechniquesPentobarbitalReceptors, GABA-ARNA, Small InterferingSodium-Potassium-Chloride SymportersSolute Carrier Family 12, Member 2SOXB1 Transcription FactorsTransfectionConceptsNPC proliferationDecreased neuronal densityTotal dendritic lengthNeonatal subventricular zoneNeural stem cell proliferationNeural progenitor cell developmentNeural progenitor proliferationShort hairpin RNADendritic complexityDendritic lengthNeuronal densityNewborn neuronsDendritic arborizationNeuron densityDendritic developmentSubventricular zoneNeuron productionCalcium responseSynaptic integrationNKCC1 knockdownPentobarbital effectsAllosteric agonistDendritic treeProgenitor cell developmentCotransporter NKCC1miR-132 Enhances Dendritic Morphogenesis, Spine Density, Synaptic Integration, and Survival of Newborn Olfactory Bulb Neurons
Pathania M, Torres-Reveron J, Yan L, Kimura T, Lin TV, Gordon V, Teng ZQ, Zhao X, Fulga TA, Van Vactor D, Bordey A. miR-132 Enhances Dendritic Morphogenesis, Spine Density, Synaptic Integration, and Survival of Newborn Olfactory Bulb Neurons. PLOS ONE 2012, 7: e38174. PMID: 22693596, PMCID: PMC3364964, DOI: 10.1371/journal.pone.0038174.Peer-Reviewed Original ResearchConceptsOlfactory bulb neuronsSynaptic integrationMiR-132Bulb neuronsSpine densityFrequency of GABAergicGlutamatergic synaptic inputsSubventricular zone neurogenesisMiR-132 overexpressionMiR-132 expressionMicroRNA miR-132Neonatal SVZTransplanted neuronsDendritic complexityNewborn neuronsNeuronal survivalPostnatal neurogenesisSynaptic inputsTransplant therapyDendritic morphogenesisNeuronsVivo electroporationSurvivalSignificant increasePlasticity program
2011
Postnatal neurogenesis generates heterotopias, olfactory micronodules and cortical infiltration following single-cell Tsc1 deletion
Feliciano DM, Quon JL, Su T, Taylor MM, Bordey A. Postnatal neurogenesis generates heterotopias, olfactory micronodules and cortical infiltration following single-cell Tsc1 deletion. Human Molecular Genetics 2011, 21: 799-810. PMID: 22068588, PMCID: PMC3263992, DOI: 10.1093/hmg/ddr511.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornCell MovementCerebral CortexDendritesElectroporationFemaleGene DeletionMaleMiceMice, TransgenicNeurogenesisNeurogliaNeuronsOlfactory BulbPeriventricular Nodular HeterotopiaSingle-Cell AnalysisTOR Serine-Threonine KinasesTuberous SclerosisTuberous Sclerosis Complex 1 ProteinTumor Suppressor ProteinsConceptsTuberous sclerosis complexSubventricular zoneBrain lesionsPostnatal subventricular zoneForebrain structuresTsc1 deletionHuman subventricular zoneCortical infiltrationNeurological symptomsNeuropsychiatric symptomsNon-invasive imagingOlfactory lesionsPostnatal neurogenesisTSC patientsPersistent infiltrationTransgenic miceAbnormal circuitsStructural abnormalitiesDendritic treeNeuronal precursorsLesionsEmbryonic neurogenesisNeurogenesisNeuronsMicronodules
2010
Function of NMDA receptors activated by astrocytic glutamate on postnatal neurogenesis
Platel JC, Bordey A. Function of NMDA receptors activated by astrocytic glutamate on postnatal neurogenesis. Médecine/sciences 2010, 26: 675-677. PMID: 20819695, DOI: 10.1051/medsci/2010268-9675.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMore neurons for respiratory adaptation: Is neurogenesis at work?
Bordey A. More neurons for respiratory adaptation: Is neurogenesis at work? Respiratory Physiology & Neurobiology 2010, 173: 118-119. PMID: 20708724, DOI: 10.1016/j.resp.2010.07.012.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsAstroglial cells in the external granular layer are precursors of cerebellar granule neurons in neonates
Silbereis J, Heintz T, Taylor MM, Ganat Y, Ment LR, Bordey A, Vaccarino F. Astroglial cells in the external granular layer are precursors of cerebellar granule neurons in neonates. Molecular And Cellular Neuroscience 2010, 44: 362-373. PMID: 20470892, PMCID: PMC2900521, DOI: 10.1016/j.mcn.2010.05.001.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornAstrocytesBasic Helix-Loop-Helix Transcription FactorsBeta-GalactosidaseCell LineageCerebellumGenes, ReporterGlial Fibrillary Acidic ProteinGreen Fluorescent ProteinsIntegrasesMiceMice, Inbred C57BLMice, TransgenicNeurogenesisNeuronsPromoter Regions, GeneticStem CellsTime FactorsConceptsExternal granule cell layerGranule cell precursorsInternal granule cell layerGranule cell layerGranule cellsRhombic lipAstroglial cellsProtein expression profilesGlial fibrillary acidic protein promoterCerebellar granule cell precursorsHuman glial fibrillary acidic protein promoterEmbryonic rhombic lipInducible Cre recombinaseNeuronal progenitor cellsReporter proteinFirst postnatal weekNeural stem cell markersLate embryogenesisCellular plasticityImmature granule cellsEarly postnatal developmentCell layerReporter geneCerebellar granule neuronsStem cell markersMicroRNA miR‐137 Regulates Neuronal Maturation by Targeting Ubiquitin Ligase Mind Bomb‐1
Smrt RD, Szulwach KE, Pfeiffer RL, Li X, Guo W, Pathania M, Teng Z, Luo Y, Peng J, Bordey A, Jin P, Zhao X. MicroRNA miR‐137 Regulates Neuronal Maturation by Targeting Ubiquitin Ligase Mind Bomb‐1. Stem Cells 2010, 28: 1060-1070. PMID: 20506192, PMCID: PMC3140955, DOI: 10.1002/stem.431.Peer-Reviewed Original ResearchConceptsNeuronal maturationMiR-137Dendritic morphogenesisSpine developmentNovel miRNA-mediated mechanismCultured primary neuronsMiR-137 overexpressionConserved target sitesMiR-137 targetsBrain-enriched microRNAYoung neuronsMicroRNA miR-137Phenotypic maturationPrimary neuronsAxonal growthMiRNA-mediated mechanismMIB1Mind bomb-1NeuronsMessenger RNAMaturationOpposite effectOverexpressionMicroRNAsNeurodevelopmentNMDA Receptors Activated by Subventricular Zone Astrocytic Glutamate Are Critical for Neuroblast Survival Prior to Entering a Synaptic Network
Platel JC, Dave KA, Gordon V, Lacar B, Rubio ME, Bordey A. NMDA Receptors Activated by Subventricular Zone Astrocytic Glutamate Are Critical for Neuroblast Survival Prior to Entering a Synaptic Network. Neuron 2010, 65: 859-872. PMID: 20346761, PMCID: PMC2861893, DOI: 10.1016/j.neuron.2010.03.009.Peer-Reviewed Original ResearchConceptsAdult-born neuronsNMDA receptorsNMDAR activitySynaptic networksNeuroblast survivalGlutamate release machineryAstrocyte-like cellsLoss of neuroblastsNeonatal electroporationSpecialized astrocytesAstrocytic glutamateOlfactory bulbVesicular releaseRelease machineryReceptorsNeuroblastsNeuronsIntercellular mechanismsSurvivalGlutamateNeuroblast apoptosisAstrocytesNeurogenesisNeurotransmittersSVZThe stem cell journey: From paradise to purgatory
Bordey A. The stem cell journey: From paradise to purgatory. Neuropharmacology 2010, 58: 833-834. PMID: 20146927, DOI: 10.1016/j.neuropharm.2010.02.004.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements