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 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
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 geneEpilepsySeizures
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
Understanding the Etiology of Tuberous Sclerosis Complex
Bordey A. Understanding the Etiology of Tuberous Sclerosis Complex. 2012 DOI: 10.21236/ada566455.Peer-Reviewed Original ResearchTuberous sclerosis complexTSC lesionsAnimal modelsDiscrete cortical lesionsGenetic multisystem disorderSevere neurological symptomsTsc1 inactivationCortical hyperexcitabilityNeurological symptomsCortical lesionsPerinatal lifeTSC patientsSeizure generationMultisystem disorderFormation of lesionsSignificant causeLesionsLesion formationEtiologyDisordersNovel technical approachHyperexcitabilityMorbidityPatientsSymptoms
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