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 behaviorInhibitionSubtypes
2018
The neurotrophic and antidepressant actions of BDNF and VEGF require interactive signaling
Deyama S, Baing E, Kato T, Li X, Duman R. The neurotrophic and antidepressant actions of BDNF and VEGF require interactive signaling. Proceedings For Annual Meeting Of The Japanese Pharmacological Society 2018, WCP2018: po2-1-62. DOI: 10.1254/jpssuppl.wcp2018.0_po2-1-62.Peer-Reviewed Original ResearchBrain-derived neurotrophic factorVascular endothelial growth factorMedial prefrontal cortexAntidepressant actionAntidepressant effectsDendritic complexityNeurotrophic factorCortical neuronsPrimary cultured cortical neuronsNovelty-suppressed feeding testNeuronal vascular endothelial growth factorGrowth factorNeuron-specific deletionCultured cortical neuronsActivity-dependent releasePrimary cortical neuronsEndothelial growth factorIntra-mPFC infusionBDNF-TrkBBDNF receptorAntidepressant responseBDNF infusionSwim testVEGF infusionNeurotrophic responses
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