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
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 neurotransmissionSestrin 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
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
2010
Post-weaning chronic social isolation produces profound behavioral dysregulation with decreases in prefrontal cortex synaptic-associated protein expression in female rats
Hermes G, Li N, Duman C, Duman R. Post-weaning chronic social isolation produces profound behavioral dysregulation with decreases in prefrontal cortex synaptic-associated protein expression in female rats. Physiology & Behavior 2010, 104: 354-359. PMID: 21185848, PMCID: PMC3387788, DOI: 10.1016/j.physbeh.2010.12.019.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAnimalsAnimals, NewbornBehavioral SymptomsBody WeightDisks Large Homolog 4 ProteinEstriolEstrusExploratory BehaviorFemaleFood DeprivationGene Expression Regulation, DevelopmentalIntracellular Signaling Peptides and ProteinsMembrane ProteinsPrefrontal CortexPregnancyRatsRats, Sprague-DawleyReceptors, AMPAReceptors, N-Methyl-D-AspartateSocial IsolationSynapsinsConceptsFemale ratsNovelty-suppressed feeding testPrefrontal cortexSocial isolationPost-weaning social isolationSynapse-related proteinsChronic social isolationFemale Sprague-DawleyEarly life stressorsSerotonergic functionGlutamate receptorsSprague-DawleyMale rodentsMaternal separationProtein PSD95Profound dysregulationNeuropsychiatric disordersBrain developmentRatsAnxiety disordersMarked deficitDeprivation resultsProtein expressionAdult animalsBiochemical effects