2020
GABA interneurons are the cellular trigger for ketamine’s rapid antidepressant actions
Gerhard DM, Pothula S, Liu RJ, Wu M, Li XY, Girgenti MJ, Taylor SR, Duman CH, Delpire E, Picciotto M, Wohleb ES, Duman RS. GABA interneurons are the cellular trigger for ketamine’s rapid antidepressant actions. Journal Of Clinical Investigation 2020, 130: 1336-1349. PMID: 31743111, PMCID: PMC7269589, DOI: 10.1172/jci130808.Peer-Reviewed Original ResearchConceptsRapid antidepressant actionsAntidepressant actionGABA interneuronsMedial prefrontal cortexCell-specific knockdownPrinciple neuronsPrefrontal cortexDeletion of GluN2BSingle subanesthetic doseBehavioral actionsAction of ketamineNMDA receptor antagonistExcitatory postsynaptic currentsCellular triggersMajor unmet needKetamine's rapid antidepressant actionsGABA subtypeGluN2B-NMDARsSST interneuronsPostsynaptic currentsReceptor antagonistDepressed patientsSubanesthetic doseExtracellular glutamateMood disorders
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
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 currents
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
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