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 ResearchConceptsGABA 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 behaviorInhibitionSubtypesGABA 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 disordersNeuron-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
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
2015
Psychological Stress Activates the Inflammasome via Release of Adenosine Triphosphate and Stimulation of the Purinergic Type 2X7 Receptor
Iwata M, Ota KT, Li XY, Sakaue F, Li N, Dutheil S, Banasr M, Duric V, Yamanashi T, Kaneko K, Rasmussen K, Glasebrook A, Koester A, Song D, Jones KA, Zorn S, Smagin G, Duman RS. Psychological Stress Activates the Inflammasome via Release of Adenosine Triphosphate and Stimulation of the Purinergic Type 2X7 Receptor. Biological Psychiatry 2015, 80: 12-22. PMID: 26831917, DOI: 10.1016/j.biopsych.2015.11.026.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnhedoniaAnimalsAnxietyBehavior, AnimalDepressionDisease Models, AnimalInflammasomesInterleukin-1betaMaleMiceMice, KnockoutNLR Family, Pyrin Domain-Containing 3 ProteinPurinergic P2Y Receptor AgonistsPurinergic P2Y Receptor AntagonistsRatsRats, Sprague-DawleyReceptors, Purinergic P2Y2Stress, PsychologicalTumor Necrosis Factor-alphaConceptsTumor necrosis factor alphaAcute restraint stressNecrosis factor alphaIL-1βRestraint stressFactor alphaExtracellular adenosine triphosphateAntagonist administrationDepressive behaviorNLRP3 inflammasomeChronic unpredictable stress exposureInflammatory cytokines IL-1βStress-related mood disordersStress-induced cytokineChronic unpredictable stressStress-induced inflammationCytokines IL-1βAdenosine triphosphateMajor depressive disorderNovel therapeutic targetInnate immune systemWestern blot analysisComorbid illnessesP2X7R antagonistsInflammasome cascade
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