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 effectorsMiceConvergent 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
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 geneThe 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 DOI: 10.7554/elife.91010.3.Peer-Reviewed Original ResearchMouse 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
2022
Current Review in Basic Science: Animal Models of Focal Cortical Dysplasia and Epilepsy
Nguyen LH, Bordey A. Current Review in Basic Science: Animal Models of Focal Cortical Dysplasia and Epilepsy. Epilepsy Currents 2022, 22: 234-240. PMID: 36187145, PMCID: PMC9483763, DOI: 10.1177/15357597221098230.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsFocal cortical dysplasiaFCD type IIAnimal modelsCortical dysplasiaMechanisms of epileptogenesisNumerous animal modelsElectroclinical featuresIntractable epilepsyType IIFCD subtypesFrequent causeCortical developmentPrevalent causeNovel therapeuticsEpilepsyEarly lifeGene mutationsClinical applicationCurrent reviewDysplasiaTechnical considerationsMTORBasic scienceCauseInhibition 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
2019
mTOR 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