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 effectorsMiceFilamin A inhibition reduces seizure activity in a mouse model of focal cortical malformations
Zhang L, Huang T, Teaw S, Nguyen LH, Hsieh LS, Gong X, Burns LH, Bordey A. Filamin A inhibition reduces seizure activity in a mouse model of focal cortical malformations. Science Translational Medicine 2020, 12 PMID: 32075941, DOI: 10.1126/scitranslmed.aay0289.Peer-Reviewed Original ResearchConceptsFocal cortical dysplasia type IITuberous sclerosis complexFocal cortical malformationsCortical malformationsSeizure frequencyReduced seizure frequencyVehicle-treated miceOnset of seizuresFilamin ALifelong epilepsyShort hairpin RNANeurological comorbiditiesNeuronal abnormalitiesSeizure activityEpilepsy treatmentSeizure onsetMouse modelAdult miceFLNA expressionPatientsCortical tissueMiceSeizuresMalformationsHairpin RNAEctopic 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 therapyConvulsive 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
2023
Advances in glioma models using in vivo electroporation to highjack neurodevelopmental processes
Zhang L, Bordey A. Advances in glioma models using in vivo electroporation to highjack neurodevelopmental processes. Biochimica Et Biophysica Acta (BBA) - Reviews On Cancer 2023, 1878: 188951. PMID: 37433417, DOI: 10.1016/j.bbcan.2023.188951.Peer-Reviewed Original ResearchCannabinoid 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
2022
Loss of PTEN phosphorylation via single point mutation alters cortical connectivity and behaviour
Binder M, Bordey A. Loss of PTEN phosphorylation via single point mutation alters cortical connectivity and behaviour. Brain 2022, 145: 3343-3344. PMID: 36148582, PMCID: PMC10233246, DOI: 10.1093/brain/awac350.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsInhibition 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 ResearchConceptsTuberous 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
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 componentsOligodendrocytesGliogenesisDiseaseNeurotransmitters
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 excitability
2016
Mammalian FMRP S499 Is Phosphorylated by CK2 and Promotes Secondary Phosphorylation of FMRP
Bartley CM, O’Keefe R, Blice-Baum A, Mihailescu MR, Gong X, Miyares L, Karaca E, Bordey A. Mammalian FMRP S499 Is Phosphorylated by CK2 and Promotes Secondary Phosphorylation of FMRP. ENeuro 2016, 3: eneuro.0092-16.2016. PMID: 27957526, PMCID: PMC5116651, DOI: 10.1523/eneuro.0092-16.2016.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, WesternCasein Kinase IICells, CulturedCerebral CortexFragile X Mental Retardation ProteinHEK293 CellsHumansMass SpectrometryMiceNaphthyridinesPhenazinesPhosphorylationProtein BiosynthesisProtein Kinase InhibitorsReceptors, Metabotropic GlutamateRecombinant ProteinsTime FactorsConceptsTranslational repressionNearby residuesProtein phosphatase 2ACasein kinase IIMental retardation proteinFMRP lossPhosphatase 2AFragile X syndromePP2A pathwaySecondary phosphorylationProtein translationKinase IIGene transcriptsFMRPBrain transcriptsFunction mutationsPhosphorylationS499X syndromeTranscriptsRepressionResiduesRecent evidenceCK2Kinase
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
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 AAbnormalitiesMTOROverexpressionSelective 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
2013
A circuitry and biochemical basis for tuberous sclerosis symptoms: from epilepsy to neurocognitive deficits
Feliciano DM, Lin TV, Hartman NW, Bartley CM, Kubera C, Hsieh L, Lafourcade C, O'Keefe RA, Bordey A. A circuitry and biochemical basis for tuberous sclerosis symptoms: from epilepsy to neurocognitive deficits. International Journal Of Developmental Neuroscience 2013, 31: 667-678. PMID: 23485365, PMCID: PMC3830611, DOI: 10.1016/j.ijdevneu.2013.02.008.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsTuberous sclerosis complexCortical lesionsBrain lesionsLoss of heterozygosityNeuronal functionNovel therapeutic targetNeuronal circuit formationMolecular mechanisms downstreamRecent mouse modelsNeurological manifestationsNeurological presentationTSC patientsBenign tumorsBrain malformationsDiscrete lesionsMouse modelNeuropsychiatric problemsTherapeutic targetSynaptic plasticityPerinatal developmentCircuit formationLesionsMTOR hyperactivityNeurocognitive deficitsPsychological impairment
2012
Newborn cortical neurons: only for neonates?
Feliciano DM, Bordey A. Newborn cortical neurons: only for neonates? Trends In Neurosciences 2012, 36: 51-61. PMID: 23062965, PMCID: PMC3534801, DOI: 10.1016/j.tins.2012.09.004.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements
2011
Gap junction‐mediated calcium waves define communication networks among murine postnatal neural progenitor cells
Lacar B, Young SZ, Platel J, Bordey A. Gap junction‐mediated calcium waves define communication networks among murine postnatal neural progenitor cells. European Journal Of Neuroscience 2011, 34: 1895-1905. PMID: 22098557, PMCID: PMC3237798, DOI: 10.1111/j.1460-9568.2011.07901.x.Peer-Reviewed Original ResearchConceptsNeural progenitor cellsNeurogenic nicheB2 cellsBlood vesselsCalcium wavesPurinergic receptor blockerProgenitor cellsPostnatal neurogenic nichesFunctional couplingPostnatal neural progenitor cellsGap junction blockersGap junction protein connexin 43Neonatal electroporationNiche astrocytesReceptor blockersProtein connexin 43Intercellular calcium wavesSubventricular zoneCells persistJunction blockersB1 cellsB cellsDye couplingDistinct entityConnexin 43