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 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
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 expressionActivity-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
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
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
Chronic 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