Featured Publications
Convulsive 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
2021
Preimplantation factor modulates oligodendrocytes by H19-induced demethylation of NCOR2
Spinelli M, Boucard C, Ornaghi S, Schoeberlein A, Irene K, Coman D, Hyder F, Zhang L, Haesler V, Bordey A, Barnea E, Paidas M, Surbek D, Mueller M. Preimplantation factor modulates oligodendrocytes by H19-induced demethylation of NCOR2. JCI Insight 2021, 6: e132335. PMID: 34676826, PMCID: PMC8564895, DOI: 10.1172/jci.insight.132335.Peer-Reviewed Original ResearchConceptsSynthetic preimplantation factorNuclear receptor corepressor 2PreImplantation FactorHypoxic-ischemic brain injuryDiffuse white matter injuryWhite matter injuryS-adenosylhomocysteine hydrolaseOligodendrocyte differentiation markersMyelin preservationPremature birthBrain recoveryBrain injuryMyelin protectionRNA H19Neurodegenerative diseasesOligodendrocyte fateDifferentiation markersInjuryH19Cellular componentsDiverse cellular componentsOligodendrocytesGliogenesisDiseaseNeurotransmittersSmall Extracellular Vesicles Control Dendritic Spine Development through Regulation of HDAC2 Signaling
Zhang L, Lin TV, Yuan Q, Sadoul R, Lam TT, Bordey A. Small Extracellular Vesicles Control Dendritic Spine Development through Regulation of HDAC2 Signaling. Journal Of Neuroscience 2021, 41: 3799-3807. PMID: 33741723, PMCID: PMC8084316, DOI: 10.1523/jneurosci.0766-20.2021.Peer-Reviewed Original ResearchConceptsSmall extracellular vesiclesRegulation of HDAC2Extracellular vesiclesSpine developmentCell-cell signalingTranscriptional programsCortical neuronsSEV releaseTranscriptional decreaseDendritic spinesNeuronal developmentNeuron developmentDendritic spine developmentLines of evidenceHDAC2Paracrine communicationAge-dependent decreaseVesiclesPopulations of neuronsRegulationLC-MS/MSHDAC2 levelsSynaptic targetsExcitatory synapsesSpine growthRab27a-Dependent Paracrine Communication Controls Dendritic Spine Formation and Sensory Responses in the Barrel Cortex
Zhang L, Zhang X, Hsieh LS, Lin TV, Bordey A. Rab27a-Dependent Paracrine Communication Controls Dendritic Spine Formation and Sensory Responses in the Barrel Cortex. Cells 2021, 10: 622. PMID: 33799820, PMCID: PMC8000154, DOI: 10.3390/cells10030622.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedDendritic SpinesExcitatory Postsynaptic PotentialsExtracellular VesiclesFemaleGene Expression Regulation, DevelopmentalGestational AgeMiceParacrine CommunicationPregnancyPyramidal CellsRab27 GTP-Binding ProteinsSensory Receptor CellsSomatosensory CortexSynaptic TransmissionVibrissaeConceptsSmall extracellular vesiclesL4 neuronsParacrine communicationExcitatory synaptic transmissionRelease of sEVsDendritic spine formationCell-autonomous effectsRisk of autismL2/3 neuronsPyramidal neuronsLayer 2/3Somatosensory cortexBarrel cortexCortical neuronsSynaptic transmissionWhisker stimulationSomatosensory informationJuvenile miceSynaptic connectivitySynaptic integrationSpine formationBrain developmentNeuronsSensory stimulationSpine development
2020
Imaging and optogenetic modulation of vascular mural cells in the live brain
Tong L, Hill RA, Damisah EC, Murray KN, Yuan P, Bordey A, Grutzendler J. Imaging and optogenetic modulation of vascular mural cells in the live brain. Nature Protocols 2020, 16: 472-496. PMID: 33299155, DOI: 10.1038/s41596-020-00425-w.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsRegional cerebral blood flowMural cellsBlood-brain barrier maintenanceCerebral ischemia mouse modelAge-related neurodegenerative diseasesCerebral blood flowSmooth muscle cell physiologyBrain blood vesselsIschemia mouse modelVascular mural cellsBrain microvesselsHigh-resolution intravital imagingVascular disordersMouse modelBlood flowMuscle cell physiologyTransgenic miceCalcium transientsAlzheimer's diseaseCalcium imagingCell subtypesBarrier maintenanceNeurodegenerative diseasesTwo-photon optogeneticsBlood vessels
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 micemTOR 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
2018
In utero electroporation-based translating ribosome affinity purification identifies age-dependent mRNA expression in cortical pyramidal neurons
Huang T, Nguyen L, Lin TV, Gong X, Zhang L, Kim GB, Sarkisian MR, Breunig JJ, Bordey A. In utero electroporation-based translating ribosome affinity purification identifies age-dependent mRNA expression in cortical pyramidal neurons. Neuroscience Research 2018, 143: 44-52. PMID: 29857015, PMCID: PMC6265126, DOI: 10.1016/j.neures.2018.05.006.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainDisks Large Homolog 4 ProteinDoublecortin ProteinElectroporationEmbryonic DevelopmentFemaleGene Expression ProfilingGene Expression Regulation, DevelopmentalGreen Fluorescent ProteinsMaleMiceOligonucleotide Array Sequence AnalysisProtein BiosynthesisPyramidal CellsRecombinant Fusion ProteinsRibosomal Protein L10Ribosomal ProteinsRNA, MessengerSomatosensory CortexSynapsinsConceptsSpecific neuronal populationsRibosomal protein L10aRibosome affinity purificationSelective biological processesNeuronal genesMolecular profileSpecific developmental patternsTarget genesAffinity purificationBiological processesGenesUtero electroporationNeuronal populationsEmbryonic day 14Molecular profilingDevelopmental patternsMRNA expression
2017
Valnoctamide Inhibits Cytomegalovirus Infection in Developing Brain and Attenuates Neurobehavioral Dysfunctions and Brain Abnormalities
Ornaghi S, Hsieh LS, Bordey A, Vergani P, Paidas MJ, van den Pol AN. Valnoctamide Inhibits Cytomegalovirus Infection in Developing Brain and Attenuates Neurobehavioral Dysfunctions and Brain Abnormalities. Journal Of Neuroscience 2017, 37: 6877-6893. PMID: 28630251, PMCID: PMC5518418, DOI: 10.1523/jneurosci.0970-17.2017.Peer-Reviewed Original ResearchConceptsAnti-CMV drugsBrain defectsNeurological outcomeCMV replicationMouse brainAvailable anti-CMV drugsHuman fetal brain cellsLong-term neurological outcomeTreatment of cytomegalovirusAdverse neurological outcomesUninfected control miceCommon infectious causeLong-term motorSecond trimester human fetusesUninfected control animalsFetal brain cellsHuman fetal astrocytesJuvenile male miceWeeks of lifeAdverse side effectsEfficacious therapeutic effectsDetectable adverse effectsNewborn mouse brainLevels of virusCMV infection
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 contributesActivating the translational repressor 4E-BP or reducing S6K-GSK3β activity prevents accelerated axon growth induced by hyperactive mTOR in vivo
Gong X, Zhang L, Huang T, Lin TV, Miyares L, Wen J, Hsieh L, Bordey A. Activating the translational repressor 4E-BP or reducing S6K-GSK3β activity prevents accelerated axon growth induced by hyperactive mTOR in vivo. Human Molecular Genetics 2015, 24: 5746-5758. PMID: 26220974, PMCID: PMC4581604, DOI: 10.1093/hmg/ddv295.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsAxonsCarrier ProteinsCell Cycle ProteinsCell Growth ProcessesEukaryotic Initiation FactorsFemaleGene Expression RegulationGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaMaleMechanistic Target of Rapamycin Complex 1MiceMultiprotein ComplexesPhosphoproteinsRibosomal Protein S6 Kinases, 90-kDaSignal TransductionTOR Serine-Threonine KinasesConceptsAxon growthNew therapeutic optionsMultiple axon formationTherapeutic optionsHippocampal neuronsHyperactive mTORNeurological disordersUtero electroporationAxonal connectivityGSK3β activityTranslational repressor 4E-BPEukaryotic initiation factor 4EMTOR complex 1Translational targetsInitiation factor 4EHyperactive mTORC1VivoDownstream effectorsGSK3βAxon formationLong-range connectivityDominant negative mutantLithium chlorideMTORopathiesMTORC1Voltage‐dependent K+ currents contribute to heterogeneity of olfactory ensheathing cells
Rela L, Piantanida AP, Bordey A, Greer CA. Voltage‐dependent K+ currents contribute to heterogeneity of olfactory ensheathing cells. Glia 2015, 63: 1646-1659. PMID: 25856239, PMCID: PMC4506201, DOI: 10.1002/glia.22834.Peer-Reviewed Original ResearchConceptsGlial cellsOlfactory nerveAxon growthVoltage-dependent potassium currentsOlfactory Ensheathing CellsSite of injuryGap junction couplingPotassium currentPotassium channelsJunction couplingInward rectifierNerveRectifier channelsCellsPhysiological propertiesLimited knowledgeInjuryOECsMembrane propertiesFascicles
2014
MEK-ERK1/2-Dependent FLNA Overexpression Promotes Abnormal Dendritic Patterning in Tuberous Sclerosis Independent of mTOR
Zhang L, Bartley CM, Gong X, Hsieh LS, Lin TV, Feliciano DM, Bordey A. MEK-ERK1/2-Dependent FLNA Overexpression Promotes Abnormal Dendritic Patterning in Tuberous Sclerosis Independent of mTOR. Neuron 2014, 84: 78-91. PMID: 25277454, PMCID: PMC4185153, DOI: 10.1016/j.neuron.2014.09.009.Peer-Reviewed Original ResearchConceptsDendritic complexityFLNA overexpressionDendritic abnormalitiesFLNA expressionDendritic patterningComplex dendritic arborsWild-type neuronsFilamin ADendritic arborsERK1/2-dependent mannerDendritic defectsNeurological defectsMEK-ERK1/2NeuronsMTOR activityNeurodevelopmental disordersNeurodevelopmental diseasesProtein filamin AAbnormalitiesMTOROverexpressionEmbryonic Cerebrospinal Fluid Nanovesicles Carry Evolutionarily Conserved Molecules and Promote Neural Stem Cell Amplification
Feliciano DM, Zhang S, Nasrallah CM, Lisgo SN, Bordey A. Embryonic Cerebrospinal Fluid Nanovesicles Carry Evolutionarily Conserved Molecules and Promote Neural Stem Cell Amplification. PLOS ONE 2014, 9: e88810. PMID: 24533152, PMCID: PMC3923048, DOI: 10.1371/journal.pone.0088810.Peer-Reviewed Original ResearchConceptsNeural stem cellsRapamycin complex 1 (mTORC1) pathwayIntracellular pathwaysStem cell amplificationInsulin-like growth factorCoordinated regulationGenetic programMicroRNA componentsExosome NanovesiclesEmbryonic CSFCell amplificationStem cellsENSCsPathwayCoordinated transferGrowth factorHuman embryosBrain developmentNanovesiclesMixed cultureAmplificationMoleculesEmbryosProteinExosomesBDNF Promotes Axon Branching of Retinal Ganglion Cells via miRNA-132 and p250GAP
Marler KJ, Suetterlin P, Dopplapudi A, Rubikaite A, Adnan J, Maiorano NA, Lowe AS, Thompson ID, Pathania M, Bordey A, Fulga T, Van Vactor DL, Hindges R, Drescher U. BDNF Promotes Axon Branching of Retinal Ganglion Cells via miRNA-132 and p250GAP. Journal Of Neuroscience 2014, 34: 969-979. PMID: 24431455, PMCID: PMC3891972, DOI: 10.1523/jneurosci.1910-13.2014.Peer-Reviewed Original ResearchConceptsBrain-derived neurotrophic factorRetinal culturesMiRNA-132Neurotrophin brain-derived neurotrophic factorRetinal ganglion cell axonsAxon branchingGanglion cell axonsRetinal ganglion cellsMouse superior colliculusBDNF actionBDNF treatmentNeurotrophic factorRGC axonsTopographic targetingGanglion cellsCell axonsSuperior colliculusExpression of microRNAsTermination zonesP250GAPProtein levelsVertebrate visual systemAxonsUpregulationMap formation
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
Neural Progenitor Cells Regulate Capillary Blood Flow in the Postnatal Subventricular Zone
Lacar B, Herman P, Platel JC, Kubera C, Hyder F, Bordey A. Neural Progenitor Cells Regulate Capillary Blood Flow in the Postnatal Subventricular Zone. Journal Of Neuroscience 2012, 32: 16435-16448. PMID: 23152626, PMCID: PMC3520061, DOI: 10.1523/jneurosci.1457-12.2012.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsAnimals, NewbornAstrocytesCalcium SignalingCapillariesCerebral VentriclesCerebrovascular CirculationElectric StimulationElectroporationFemaleFluorescent Antibody TechniqueImage Processing, Computer-AssistedLaser-Doppler FlowmetryMaleMiceMuscle TonusMuscle, Smooth, VascularNeural Stem CellsPericytesVasoconstrictionVasodilationConceptsNeural progenitor cellsSubventricular zoneB cellsBlood flowSVZ cellsPurinergic receptorsPostnatal subventricular zoneVascular responsesCapillary constrictionTransgenic miceElectrical stimulationCalcium increaseBlood flow increasesLaser Doppler flowmetryCapillary blood flowAstrocyte-like cellsReceptor agonist UTPNeonatal electroporationNeurometabolic couplingIntraventricular injectionVasodilating factorsAcute slicesYoung miceDoppler flowmetryHemodynamic responseNKCC1 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 NKCC1Transient mGlu5R inhibition enhances the survival of granule cell precursors in the neonatal cerebellum
Kubera C, Hernandez AL, Heng V, Bordey A. Transient mGlu5R inhibition enhances the survival of granule cell precursors in the neonatal cerebellum. Neuroscience 2012, 219: 271-279. PMID: 22677205, PMCID: PMC3402690, DOI: 10.1016/j.neuroscience.2012.05.064.Peer-Reviewed Original ResearchConceptsExternal germinal layerGranule cell precursorsGranule cellsS-phase marker bromodeoxyuridineMetabotropic glutamate receptor 5Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) stainingTransferase dUTP nick end labeling stainingCell precursorsDUTP nick end labeling stainingNick end labeling stainingGlutamate receptor 5Postnatal day 2Proliferative granule cell precursorsEnd labeling stainingCerebellar granule cellsAcute slicesAbundant neuronsBrdU injectionLabeling stainingVivo treatmentReceptor 5Day 2Vivo injectionSpecific receptorsClonal expansion