2019
Sestrin 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