2020
Neuron-specific deletion of VEGF or its receptor Flk-1 impairs recognition memory
Deyama S, Li XY, Duman RS. Neuron-specific deletion of VEGF or its receptor Flk-1 impairs recognition memory. European Neuropsychopharmacology 2020, 31: 145-151. PMID: 31902568, DOI: 10.1016/j.euroneuro.2019.11.002.Peer-Reviewed Original ResearchConceptsNeuron-specific deletionCognitive impairmentFlk-1Chemotherapy-induced cognitive impairmentNovel object recognition testVascular endothelial growth factorObject recognition testConditional knockout miceEndothelial growth factorFetal liver kinase-1Liver kinase-1Impairs recognition memoryPerivascular macrophagesRecognition memoryVEGF inhibitorsPreclinical studiesKnockout miceEndothelial cellsMiceGrowth factorPleiotropic factorLong-term recognition memoryVEGFImpairmentVEGF Signaling
2019
Role of Neuronal VEGF Signaling in the Prefrontal Cortex in the Rapid Antidepressant Effects of Ketamine
Deyama S, Bang E, Wohleb ES, Li XY, Kato T, Gerhard DM, Dutheil S, Dwyer JM, Taylor SR, Picciotto MR, Duman RS. Role of Neuronal VEGF Signaling in the Prefrontal Cortex in the Rapid Antidepressant Effects of Ketamine. American Journal Of Psychiatry 2019, 176: 388-400. PMID: 30606046, PMCID: PMC6494682, DOI: 10.1176/appi.ajp.2018.17121368.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, NeutralizingBehavior, AnimalExcitatory Amino Acid AntagonistsGene Knockdown TechniquesGene Knockout TechniquesIn Vitro TechniquesKetamineMiceNeuronsPrefrontal CortexQuinazolinesSignal TransductionVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2ConceptsNeuronal vascular endothelial growth factorVascular endothelial growth factorMedial prefrontal cortexRapid antidepressant actionsAntidepressant actionIntra-mPFC infusionSystemic ketamineBehavioral actionsFlk-1Conventional monoamine-based antidepressantsPrefrontal cortexRole of VEGFRapid antidepressant effectsTreatment-resistant depressionMethyl-d-aspartate receptor antagonist ketamineNeuron-specific deletionMonoamine-based antidepressantsNeuron-specific knockoutViral-mediated knockdownEndothelial growth factorVEGF-Flk-1Synaptogenic actionsAntidepressant effectsSynaptogenic effectsLocal knockdown
2018
Neurotrophic and Antidepressant Actions of Brain-Derived Neurotrophic Factor Require Vascular Endothelial Growth Factor
Deyama S, Bang E, Kato T, Li XY, Duman RS. Neurotrophic and Antidepressant Actions of Brain-Derived Neurotrophic Factor Require Vascular Endothelial Growth Factor. Biological Psychiatry 2018, 86: 143-152. PMID: 30712809, PMCID: PMC6597338, DOI: 10.1016/j.biopsych.2018.12.014.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, BlockingAntidepressive AgentsBehavior, AnimalBrain-Derived Neurotrophic FactorCerebral CortexGene DeletionMaleMiceMice, Inbred C57BLMicroinjectionsNeuronsNootropic AgentsPrefrontal CortexPrimary Cell CultureVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2ConceptsBrain-derived neurotrophic factorVascular endothelial growth factorRole of VEGFAntidepressant-like actionPrimary cortical neuronsNeurotrophic actionsEndothelial growth factorMedial prefrontal cortexRelease of VEGFAntidepressant actionCortical neuronsAction of BDNFInfluence of BDNFRole of BDNFRat primary cortical neuronsGrowth factorAntidepressant behavioral actionsNeuron-specific deletionActivity-dependent releaseAction of VEGFBDNF inductionDendrite complexityNeurotrophic factorReceptor antagonistVEGF expressionActivity-dependent brain-derived neurotrophic factor signaling is required for the antidepressant actions of (2R,6R)-hydroxynorketamine
Fukumoto K, Fogaça M, Liu RJ, Duman C, Kato T, Li XY, Duman RS. Activity-dependent brain-derived neurotrophic factor signaling is required for the antidepressant actions of (2R,6R)-hydroxynorketamine. Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 116: 297-302. PMID: 30559184, PMCID: PMC6320534, DOI: 10.1073/pnas.1814709116.Peer-Reviewed Original ResearchConceptsActivity-dependent BDNF releaseAntidepressant effectsAntidepressant actionBDNF releaseActivity-dependent brain-derived neurotrophic factorL-type voltage-dependent CaSynaptic functionBrain-derived neurotrophic factorMajor depressive disorder patientsMethyl-d-aspartate (NMDA) receptor antagonistIntra-mPFC microinjectionRapid antidepressant effectsDepressive disorder patientsTreatment of MDDBDNF Val66Met allelesVoltage-dependent CaIntra-mPFC infusionMetabolite of ketamineDownstream TrkBNeurotrophic factorReceptor antagonistNMDA receptorsMolecular signaling mechanismsRodent modelsDisorder patients
2011
Glutamate N-methyl-D-aspartate Receptor Antagonists Rapidly Reverse Behavioral and Synaptic Deficits Caused by Chronic Stress Exposure
Li N, Liu RJ, Dwyer JM, Banasr M, Lee B, Son H, Li XY, Aghajanian G, Duman RS. Glutamate N-methyl-D-aspartate Receptor Antagonists Rapidly Reverse Behavioral and Synaptic Deficits Caused by Chronic Stress Exposure. Biological Psychiatry 2011, 69: 754-761. PMID: 21292242, PMCID: PMC3068225, DOI: 10.1016/j.biopsych.2010.12.015.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBehavior, AnimalBlotting, WesternChoice BehaviorDendritic SpinesElectrophysiologyExcitatory Amino Acid AntagonistsKetamineNeuronsPhenolsPiperidinesPrefrontal CortexRatsRats, Sprague-DawleyReceptors, N-Methyl-D-AspartateSignal TransductionSirolimusStress, PhysiologicalStress, PsychologicalSynapsesSynaptic TransmissionConceptsGlutamate N-methyl-d-aspartate (NMDA) receptor antagonistN-methyl-D-aspartate receptor antagonistNMDA receptor antagonistReceptor antagonistLayer V pyramidal neuronsChronic unpredictable stress modelMammalian targetStress exposureDepressant-like behaviorLong-term stress exposurePathophysiology of depressionRapid antidepressant actionsSelective NMDA receptorChronic stress exposurePrefrontal cortex neuronsAntidepressant actionAcute treatmentChronic administrationSynaptic deficitsPyramidal neuronsSpine densityRo 25Cortex neuronsFunctional deficitsNMDA receptors
2010
mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists
Li N, Lee B, Liu RJ, Banasr M, Dwyer JM, Iwata M, Li XY, Aghajanian G, Duman RS. mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists. Science 2010, 329: 959-964. PMID: 20724638, PMCID: PMC3116441, DOI: 10.1126/science.1190287.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntidepressive AgentsDendritic SpinesDepressionIntracellular Signaling Peptides and ProteinsKetamineMaleNeuronsNeuropeptidesPhenolsPiperidinesProtein BiosynthesisProtein Serine-Threonine KinasesRatsRats, Sprague-DawleyReceptors, N-Methyl-D-AspartateSignal TransductionSirolimusSynapsesTime FactorsTOR Serine-Threonine KinasesConceptsTreatment-resistant depressed patientsBlockade of mTORFast antidepressant actionAction of ketamineRapid antidepressant effectsRapid antidepressant responseEffects of ketamineModel of depressionAntidepressant actionAntidepressant effectsAntidepressant responseKetamine inductionStandard medicationSynaptic deficitsKetamine administrationDepressed patientsSpine synapsesNMDA antagonistsMood disordersSynapse formationKetamineMammalian targetPrefrontal cortexRapamycin (mTOR) pathwayPossible new approach
2009
Eszopiclone and fluoxetine enhance the survival of newborn neurons in the adult rat hippocampus
Su XW, Li XY, Banasr M, Duman RS. Eszopiclone and fluoxetine enhance the survival of newborn neurons in the adult rat hippocampus. The International Journal Of Neuropsychopharmacology 2009, 12: 1421-1428. PMID: 19775501, PMCID: PMC3677220, DOI: 10.1017/s1461145709990629.Peer-Reviewed Original ResearchConceptsNewborn neuronsAntidepressant actionSerotonin uptake inhibitorAdult rat hippocampusAdult hippocampusCombined administrationDorsal hippocampusRat hippocampusPreclinical studiesAdult ratsUptake inhibitorFluoxetineHippocampusNewborn cellsClinical researchEszopicloneBehavioral actionsNeuronsSurvivalAdditive effectNovel mechanismProliferationAntidepressantsPatientsChronicChronic treatment with AMPA receptor potentiator Org 26576 increases neuronal cell proliferation and survival in adult rodent hippocampus
Su XW, Li XY, Banasr M, Koo JW, Shahid M, Henry B, Duman RS. Chronic treatment with AMPA receptor potentiator Org 26576 increases neuronal cell proliferation and survival in adult rodent hippocampus. Psychopharmacology 2009, 206: 215-222. PMID: 19603152, DOI: 10.1007/s00213-009-1598-0.Peer-Reviewed Original ResearchConceptsOrg 26576Neuronal cell proliferationHippocampal neurogenesisChronic administrationAntidepressant propertiesCell proliferationDentate gyrusPrelimbic cortexMethodsMale Sprague–Dawley ratsAdult rodent hippocampusLast drug injectionDaily intraperitoneal injectionsSprague-Dawley ratsIsoxazolepropionic acid receptor potentiatorsDifferentiation of neuronsRate of survivalResultsAcute administrationAvailable antidepressantsProgenitor cell proliferationChronic treatmentCurrent antidepressantsIntraperitoneal injectionDrug injectionAdult ratsReceptor potentiators
2007
Chronic Unpredictable Stress Decreases Cell Proliferation in the Cerebral Cortex of the Adult Rat
Banasr M, Valentine GW, Li XY, Gourley SL, Taylor JR, Duman RS. Chronic Unpredictable Stress Decreases Cell Proliferation in the Cerebral Cortex of the Adult Rat. Biological Psychiatry 2007, 62: 496-504. PMID: 17585885, DOI: 10.1016/j.biopsych.2007.02.006.Peer-Reviewed Original ResearchConceptsChronic unpredictable stressCell proliferationAdult ratsPrefrontal cortexChronic antidepressant administrationNumber of gliaNumber of oligodendrocytesPotential cellular mechanismsCortical cell proliferationDecrease cell proliferationAntidepressant administrationCUS paradigmGlial reductionCerebral cortexSucrose preferenceDepressed patientsMorphologic findingsPostmortem studiesUnpredictable stressDepressed subjectsBrain tissueChronic stressEndothelial cellsCellular actionsCortex