2020
Inhibition of GABA interneurons in the mPFC is sufficient and necessary for rapid antidepressant responses
Fogaça MV, Wu M, Li C, Li XY, Picciotto MR, Duman RS. Inhibition of GABA interneurons in the mPFC is sufficient and necessary for rapid antidepressant responses. Molecular Psychiatry 2020, 26: 3277-3291. PMID: 33070149, PMCID: PMC8052382, DOI: 10.1038/s41380-020-00916-y.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntidepressive AgentsDepressive Disorder, MajorGamma-Aminobutyric AcidInterneuronsMaleMiceParvalbuminsPrefrontal CortexConceptsGABA interneuronsRapid antidepressant responseMajor depressive disorderAntidepressant effectsSynaptic plasticityAntidepressant responseRapid-acting antidepressantsAcetylcholine muscarinic receptor antagonistMuscarinic receptor antagonistCortical brain areasEffects of scopolamineAntidepressant actionChemogenetic inhibitionGABAergic interneuronsReceptor antagonistDepressive disorderMale miceInterneuron subtypesBrain areasInterneuronsMPFCTransient inhibitionAffective behaviorInhibitionSubtypesMedial PFC AMPA receptor and BDNF signaling are required for the rapid and sustained antidepressant-like effects of 5-HT1A receptor stimulation
Fukumoto K, Fogaça M, Liu RJ, Duman CH, Li XY, Chaki S, Duman RS. Medial PFC AMPA receptor and BDNF signaling are required for the rapid and sustained antidepressant-like effects of 5-HT1A receptor stimulation. Neuropsychopharmacology 2020, 45: 1725-1734. PMID: 32396921, PMCID: PMC7419563, DOI: 10.1038/s41386-020-0705-0.Peer-Reviewed Original ResearchConceptsBrain-derived neurotrophic factorAntidepressant-like effectsMajor depressive disorderMedial prefrontal cortexMPFC infusionSelective stimulationReceptor antagonistAMPA receptorsNon-competitive N-methyl-D-aspartate (NMDA) receptor antagonistTreatment of MDDN-methyl-D-aspartate receptor antagonistSynaptic functionAntidepressant-like actionNovelty-suppressed feedingAMPA receptor antagonistGlutamate AMPA receptorsMPFC 5Antidepressant effectsNeurotrophic factorReceptor agonistDepressive disorderSerotonergic systemReceptor stimulationReceptor activationSynaptic proteins
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 expression
2017
BDNF release and signaling are required for the antidepressant actions of GLYX-13
Kato T, Fogaça MV, Deyama S, Li XY, Fukumoto K, Duman RS. BDNF release and signaling are required for the antidepressant actions of GLYX-13. Molecular Psychiatry 2017, 23: 2007-2017. PMID: 29203848, PMCID: PMC5988860, DOI: 10.1038/mp.2017.220.Peer-Reviewed Original ResearchConceptsGLYX-13Antidepressant actionAntidepressant effectsIntra-medial prefrontal cortex infusionN-methyl-d-aspartate modulatorsActivation of VDCCsAntidepressant behavioral actionsConventional antidepressant medicationRapid antidepressant actionsActivity-dependent releaseVoltage-dependent Ca2Partial agonist propertiesPreclinical rodent modelsBDNF Val66Met allelesBDNF-TrkBAntidepressant medicationBDNF releaseGlutamatergic compoundsMonoaminergic systemsDepressed patientsRodent modelsAgonist propertiesVal66Met alleleTherapeutic efficacyMutant mice
2011
Brain-Derived Neurotrophic Factor Val66Met Allele Impairs Basal and Ketamine-Stimulated Synaptogenesis in Prefrontal Cortex
Liu RJ, Lee FS, Li XY, Bambico F, Duman RS, Aghajanian GK. Brain-Derived Neurotrophic Factor Val66Met Allele Impairs Basal and Ketamine-Stimulated Synaptogenesis in Prefrontal Cortex. Biological Psychiatry 2011, 71: 996-1005. PMID: 22036038, PMCID: PMC3290730, DOI: 10.1016/j.biopsych.2011.09.030.Peer-Reviewed Original ResearchMeSH KeywordsAllelesAnimalsBrain-Derived Neurotrophic FactorDendritesDepressive Disorder, MajorExcitatory Amino Acid AntagonistsExcitatory Postsynaptic PotentialsKetamineMiceMice, TransgenicPatch-Clamp TechniquesPolymorphism, GeneticPrefrontal CortexPyramidal CellsReceptors, N-Methyl-D-AspartateRNA, MessengerSynapsesConceptsBDNF messenger RNAMet miceVal/MetPrefrontal cortexSynaptic deficitsPyramidal cellsBrain-derived neurotrophic factor (BDNF) Val66Met polymorphismNeurotrophic factor Val66Met polymorphismLayer V pyramidal cellsMet alleleDistal apical dendritesExcitatory postsynaptic currentsWhole-cell recordingsPFC pyramidal cellsBDNF Met alleleMet/MetTwo-photon laser scanningMessenger RNAAspartate antagonistAntidepressant actionAntidepressant responseSpine densityVal66Met polymorphismApical dendritesPostsynaptic currentsGlutamate 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