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
2022
Inhibition of MEK-ERK signaling reduces seizures in two mouse models of tuberous sclerosis complex
Nguyen LH, Leiser SC, Song D, Brunner D, Roberds SL, Wong M, Bordey A. Inhibition of MEK-ERK signaling reduces seizures in two mouse models of tuberous sclerosis complex. Epilepsy Research 2022, 181: 106890. PMID: 35219048, PMCID: PMC8930622, DOI: 10.1016/j.eplepsyres.2022.106890.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDisease Models, AnimalHumansMiceMitogen-Activated Protein Kinase KinasesSeizuresSignal TransductionTuberous SclerosisConceptsTuberous sclerosis complexMouse modelTSC mouse modelsDevelopmental brain malformationsMEK-ERKNovel treatment targetsMEK inhibitor PD0325901Intractable epilepsySeizure activityTSC patientsSeizure suppressionBrain malformationsMTOR inhibitorsTreatment targetsMEK-ERK activitySeizuresTSC neuropathologyPotential alternative strategyMEK-ERK inhibitionInhibitor PD0325901Monogenic disordersInhibitionMTORTreatmentEverolimus
2021
Small 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 growth
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
Activating 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 chlorideMTORopathiesMTORC1PreImplantation Factor bolsters neuroprotection via modulating Protein Kinase A and Protein Kinase C signaling
Mueller M, Schoeberlein A, Zhou J, Joerger-Messerli M, Oppliger B, Reinhart U, Bordey A, Surbek D, Barnea ER, Huang Y, Paidas M. PreImplantation Factor bolsters neuroprotection via modulating Protein Kinase A and Protein Kinase C signaling. Cell Death & Differentiation 2015, 22: 2078-2086. PMID: 25976303, PMCID: PMC4816111, DOI: 10.1038/cdd.2015.55.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBcl-Associated Death ProteinBrain InjuriesCell Line, TumorCell SurvivalCyclic AMPCyclic AMP Response Element-Binding ProteinCyclic AMP-Dependent Protein KinasesDisease Models, AnimalGAP-43 ProteinMiceMicroRNAsNeuroprotective AgentsPeptidesProtein Kinase CProto-Oncogene Proteins c-bcl-2RatsRNA InterferenceSignal TransductionToll-Like Receptor 4ConceptsPreImplantation FactorCentral nervous system damageExperimental autoimmune encephalomyelitisPerinatal brain injuryBrain injury modelNervous system damageExpression of GAP43Autoimmune encephalomyelitisTLR4 expressionNeuronal lossPotential clinical applicationsCNS diseaseNeuronal deathBrain injuryClinical trialsInjury modelFast-track approvalProtective effectRodent modelsGAP-43NeuroprotectionSystem damageNeuronal growthProtein kinaseCortical architecture
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 geneEpilepsySeizuresFMRP S499 Is Phosphorylated Independent of mTORC1-S6K1 Activity
Bartley CM, O’Keefe R, Bordey A. FMRP S499 Is Phosphorylated Independent of mTORC1-S6K1 Activity. PLOS ONE 2014, 9: e96956. PMID: 24806451, PMCID: PMC4013076, DOI: 10.1371/journal.pone.0096956.Peer-Reviewed Original ResearchEmbryonic 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 cultureAmplificationMoleculesEmbryosProteinExosomes
2009
GABA’s Control of Stem and Cancer Cell Proliferation in Adult Neural and Peripheral Niches
Young SZ, Bordey A. GABA’s Control of Stem and Cancer Cell Proliferation in Adult Neural and Peripheral Niches. Physiology 2009, 24: 171-185. PMID: 19509127, PMCID: PMC2931807, DOI: 10.1152/physiol.00002.2009.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAdult Stem CellsAnimalsCell DivisionEmbryonic Stem CellsGamma-Aminobutyric AcidHumansNeoplasmsSignal TransductionConceptsStem cellsGamma-amino butyric acidProliferation of pluripotentAdult stem cellsNeural stem cellsAdult tissuesCancer cell proliferationRegulation of secretionTumor stem cellsTumor cellsCell proliferationAdult neuralProliferationCellsGABA controlPeripheral organsGABAergic signalingPeripheral nichesNervous systemMitotic activityPluripotentButyric acidNicheSignalingRegulationGABA increases Ca2+ in cerebellar granule cell precursors via depolarization: Implications for proliferation
Dave KA, Bordey A. GABA increases Ca2+ in cerebellar granule cell precursors via depolarization: Implications for proliferation. IUBMB Life 2009, 61: 496-503. PMID: 19391160, PMCID: PMC2675662, DOI: 10.1002/iub.185.Peer-Reviewed Original ResearchConceptsGamma-aminobutyric acidRole of GABAVertebrate central nervous systemComplement of receptorsCerebellar granule cell precursorsCell precursorsGranule cell precursorsDevelopmental processesMetabotropic glutamate receptorsCentral nervous systemCell proliferationAdult mammalsNovel targetAmino acid glutamatePharmacological regulationCurrent knowledgeGlutamate receptorsNeural cancersNervous systemCerebellar tumorsCalcium increaseReceptorsProliferationMammalsNovel data
2007
GABA and glutamate signaling: homeostatic control of adult forebrain neurogenesis
Platel JC, Lacar B, Bordey A. GABA and glutamate signaling: homeostatic control of adult forebrain neurogenesis. Journal Of Molecular Histology 2007, 38: 303-311. PMID: 17554632, PMCID: PMC2556597, DOI: 10.1007/s10735-007-9103-8.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsSubventricular zoneOlfactory bulb interneuronsGABAergic signalingGlutamate receptorsBulb interneuronsForebrain neurogenesisAMPA/kainate receptorsMetabotropic glutamate receptorsNeurogenic subventricular zoneRole of glutamateHomeostatic controlIonotropic glutamate receptorsEmbryonic cortical developmentSVZ neuroblastsNeurotransmitter GABASVZ cellsCortical developmentKainate receptorsGABA transporter subtypesNeurotransmitter glutamateGABA clearanceGABATransporter subtypesReceptorsInterneurons
2006
Enigmatic GABAergic networks in adult neurogenic zones
Bordey A. Enigmatic GABAergic networks in adult neurogenic zones. Brain Research Reviews 2006, 53: 124-134. PMID: 16949673, DOI: 10.1016/j.brainresrev.2006.07.004.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAdult neurogenic zonesNeurogenic zonesGABAergic networksGABAergic signalingAdult neurogenic regionsGABA actionSubventricular zoneNeuronal activityNeurogenic regionsReceptor activationImmature cellsProgenitor cellsUnique cellular propertiesNetwork activitySignalingCellsCellular propertiesReviewAdult Neurogenesis: Basic Concepts of Signaling
Bordey A. Adult Neurogenesis: Basic Concepts of Signaling. Cell Cycle 2006, 5: 722-728. PMID: 16582623, DOI: 10.4161/cc.5.7.2614.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAgingCell CommunicationCell DifferentiationHumansModels, NeurologicalNeuronsSignal TransductionStem CellsConceptsAdult neurogenesisMotor memory formationBrain injuryPersistent neurogenesisNeurogenic environmentAdult brainNeurogenic regionsNeuroglial networksNeurogenesisEmbryonic neurogenesisIntegrative propertiesMemory formationExtracellular matrix moleculesCell communicationBrainRecent findingsCellsExamples of cellsMatrix moleculesInjury