Catharine Duman, PhD
Cards
About
Research
Publications
2020
Medial 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 proteinsGABA 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
Ketamine rapidly reverses stress-induced impairments in GABAergic transmission in the prefrontal cortex in male rodents
Ghosal S, Duman CH, Liu RJ, Wu M, Terwilliger R, Girgenti MJ, Wohleb E, Fogaca MV, Teichman EM, Hare B, Duman RS. Ketamine rapidly reverses stress-induced impairments in GABAergic transmission in the prefrontal cortex in male rodents. Neurobiology Of Disease 2019, 134: 104669. PMID: 31707118, DOI: 10.1016/j.nbd.2019.104669.Peer-Reviewed Original ResearchConceptsChronic unpredictable stressMedial prefrontal cortexInhibitory post-synaptic currentsGABAergic transmissionSingle doseMale rodentsPrefrontal cortexImbalance of inhibitoryMPFC pyramidal neuronsDepressive-like behaviorDepression-like behaviorStress-induced impairmentModel of depressionPost-synaptic currentsPrecise cellular mechanismsGABAergic proteinsAntidepressant ketamineSynaptic deficitsGABAergic synapsesPyramidal neuronsSynaptic markersGABA markersGlutamate neurotransmissionDepressive behaviorGABA neurotransmissionN-Methyl-D-aspartate receptor antagonist d-methadone produces rapid, mTORC1-dependent antidepressant effects
Fogaça MV, Fukumoto K, Franklin T, Liu RJ, Duman CH, Vitolo OV, Duman RS. N-Methyl-D-aspartate receptor antagonist d-methadone produces rapid, mTORC1-dependent antidepressant effects. Neuropsychopharmacology 2019, 44: 2230-2238. PMID: 31454827, PMCID: PMC6898593, DOI: 10.1038/s41386-019-0501-x.Peer-Reviewed Original ResearchConceptsNovelty-suppressed feeding testMedial prefrontal cortexD-methadoneNMDA receptor antagonistAntidepressant actionPhospho-p70S6 kinaseReceptor antagonistN-methyl-D-aspartate receptorsNoncompetitive NMDA receptor antagonistTreatment-resistant patientsChronic unpredictable stressRapid antidepressant actionsDissociative side effectsPrimary cortical culturesMeasures of anhedoniaKetamine inducesAvailable antidepressantsTolerability profileAntidepressant effectsBDNF releaseAntidepressant responseResistant patientsFavorable safetySingle doseCortical culturesSestrin modulator NV-5138 produces rapid antidepressant effects via direct mTORC1 activation
Kato T, Pothula S, Liu RJ, Duman CH, Terwilliger R, Vlasuk GP, Saiah E, Hahm S, Duman RS. Sestrin modulator NV-5138 produces rapid antidepressant effects via direct mTORC1 activation. Journal Of Clinical Investigation 2019, 129: 2542-2554. PMID: 30990795, PMCID: PMC6546461, DOI: 10.1172/jci126859.Peer-Reviewed Original ResearchConceptsMedial prefrontal cortexRapid acting antidepressantsActing antidepressantsAntidepressant actionAntidepressant effectsBDNF releaseActivity-dependent BDNF releaseRapid antidepressant effectsBlood-brain barrierChronic stress exposureSynaptic deficitsBDNF polymorphismSingle doseBrain barrierSynapse numberPreclinical studiesPharmacological modulationNeuronal activityChronic stressPrefrontal cortexRapid synapticStress exposureBehavioral responsesAmino acid leucineAntidepressants
2018
Activity-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
2017
Stress-Induced Neuronal Colony Stimulating Factor 1 Provokes Microglia-Mediated Neuronal Remodeling and Depressive-like Behavior
Wohleb ES, Terwilliger R, Duman CH, Duman RS. Stress-Induced Neuronal Colony Stimulating Factor 1 Provokes Microglia-Mediated Neuronal Remodeling and Depressive-like Behavior. Biological Psychiatry 2017, 83: 38-49. PMID: 28697890, PMCID: PMC6506225, DOI: 10.1016/j.biopsych.2017.05.026.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnxietyChronic DiseaseDepressive DisorderDisease Models, AnimalFemaleMacrophage Colony-Stimulating FactorMaleMice, Inbred C57BLMice, TransgenicMicrogliaNeuronal PlasticityNeuronsPhagocytosisPrefrontal CortexReceptor, Macrophage Colony-Stimulating FactorRNA, MessengerSex CharacteristicsStress, PsychologicalUncertaintyConceptsDepressive-like behaviorChronic unpredictable stressMedial prefrontal cortexDendritic spine densityNeuronal remodelingSynaptic deficitsDevelopment of anxietyMessenger RNA levelsPrefrontal cortexSpine densityFemale miceFunctional changesStress exposureNeuron-microglia interactionsRNA levelsChronic stress exposureStress-induced elevationPostmortem dorsolateral prefrontal cortexDorsolateral prefrontal cortexBehavioral consequencesNeuronal atrophyPyramidal neuronsMicroglia functionMale miceUnpredictable stress
2016
GLYX-13 Produces Rapid Antidepressant Responses with Key Synaptic and Behavioral Effects Distinct from Ketamine
Liu RJ, Duman C, Kato T, Hare B, Lopresto D, Bang E, Burgdorf J, Moskal J, Taylor J, Aghajanian G, Duman RS. GLYX-13 Produces Rapid Antidepressant Responses with Key Synaptic and Behavioral Effects Distinct from Ketamine. Neuropsychopharmacology 2016, 42: 1231-1242. PMID: 27634355, PMCID: PMC5437877, DOI: 10.1038/npp.2016.202.Peer-Reviewed Original ResearchConceptsPsychotomimetic side effectsGLYX-13Prefrontal cortexSide effectsGlycine-site partial agonist propertiesLayer V pyramidal neuronsSerial reaction time taskAntidepressant behavioral actionsBehavioral actionsRapid antidepressant effectsRapid acting antidepressantsRapid antidepressant responseApical dendritic tuftsMedial PFCNMDA receptor modulatorsPartial agonist propertiesMedial prefrontal cortexActing antidepressantsAntidepressant actionAntidepressant effectsThalamocortical synapsesAntidepressant responsePyramidal neuronsSingle doseDendritic tufts
2015
Spine synapse remodeling in the pathophysiology and treatment of depression
Duman CH, Duman RS. Spine synapse remodeling in the pathophysiology and treatment of depression. Neuroscience Letters 2015, 601: 20-29. PMID: 25582786, PMCID: PMC4497940, DOI: 10.1016/j.neulet.2015.01.022.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsSynaptic protein synthesisPrefrontal cortexSpine densityTreatment-resistant MDD patientsChronic antidepressant treatmentSpine synapse numberControl of moodChronic stress modelSynapse connectivityTreatment of depressionLimbic brain regionsPFC of rodentsRapid therapeutic actionDendrite complexityRegion-specific effectsSynaptogenic hypothesisAntidepressant treatmentAntidepressant ketamineBDNF regulationNeurotrophic factorMDD patientsDepressed patientsSynapse alterationsSynapse numberFunctional abnormalities
2014
REDD1 is essential for stress-induced synaptic loss and depressive behavior
Ota KT, Liu RJ, Voleti B, Maldonado-Aviles JG, Duric V, Iwata M, Dutheil S, Duman C, Boikess S, Lewis DA, Stockmeier CA, DiLeone RJ, Rex C, Aghajanian GK, Duman RS. REDD1 is essential for stress-induced synaptic loss and depressive behavior. Nature Medicine 2014, 20: 531-535. PMID: 24728411, PMCID: PMC4016190, DOI: 10.1038/nm.3513.Peer-Reviewed Original Research