2024
Single-cell genomics and regulatory networks for 388 human brains
Emani P, Liu J, Clarke D, Jensen M, Warrell J, Gupta C, Meng R, Lee C, Xu S, Dursun C, Lou S, Chen Y, Chu Z, Galeev T, Hwang A, Li Y, Ni P, Zhou X, Bakken T, Bendl J, Bicks L, Chatterjee T, Cheng L, Cheng Y, Dai Y, Duan Z, Flaherty M, Fullard J, Gancz M, Garrido-Martín D, Gaynor-Gillett S, Grundman J, Hawken N, Henry E, Hoffman G, Huang A, Jiang Y, Jin T, Jorstad N, Kawaguchi R, Khullar S, Liu J, Liu J, Liu S, Ma S, Margolis M, Mazariegos S, Moore J, Moran J, Nguyen E, Phalke N, Pjanic M, Pratt H, Quintero D, Rajagopalan A, Riesenmy T, Shedd N, Shi M, Spector M, Terwilliger R, Travaglini K, Wamsley B, Wang G, Xia Y, Xiao S, Yang A, Zheng S, Gandal M, Lee D, Lein E, Roussos P, Sestan N, Weng Z, White K, Won H, Girgenti M, Zhang J, Wang D, Geschwind D, Gerstein M, Akbarian S, Abyzov A, Ahituv N, Arasappan D, Almagro Armenteros J, Beliveau B, Berretta S, Bharadwaj R, Bhattacharya A, Brennand K, Capauto D, Champagne F, Chatzinakos C, Chen H, Cheng L, Chess A, Chien J, Clement A, Collado-Torres L, Cooper G, Crawford G, Dai R, Daskalakis N, Davila-Velderrain J, Deep-Soboslay A, Deng C, DiPietro C, Dracheva S, Drusinsky S, Duong D, Eagles N, Edelstein J, Galani K, Girdhar K, Goes F, Greenleaf W, Guo H, Guo Q, Hadas Y, Hallmayer J, Han X, Haroutunian V, He C, Hicks S, Ho M, Ho L, Huang Y, Huuki-Myers L, Hyde T, Iatrou A, Inoue F, Jajoo A, Jiang L, Jin P, Jops C, Jourdon A, Kellis M, Kleinman J, Kleopoulos S, Kozlenkov A, Kriegstein A, Kundaje A, Kundu S, Li J, Li M, Lin X, Liu S, Liu C, Loupe J, Lu D, Ma L, Mariani J, Martinowich K, Maynard K, Myers R, Micallef C, Mikhailova T, Ming G, Mohammadi S, Monte E, Montgomery K, Mukamel E, Nairn A, Nemeroff C, Norton S, Nowakowski T, Omberg L, Page S, Park S, Patowary A, Pattni R, Pertea G, Peters M, Pinto D, Pochareddy S, Pollard K, Pollen A, Przytycki P, Purmann C, Qin Z, Qu P, Raj T, Reach S, Reimonn T, Ressler K, Ross D, Rozowsky J, Ruth M, Ruzicka W, Sanders S, Schneider J, Scuderi S, Sebra R, Seyfried N, Shao Z, Shieh A, Shin J, Skarica M, Snijders C, Song H, State M, Stein J, Steyert M, Subburaju S, Sudhof T, Snyder M, Tao R, Therrien K, Tsai L, Urban A, Vaccarino F, van Bakel H, Vo D, Voloudakis G, Wang T, Wang S, Wang Y, Wei Y, Weimer A, Weinberger D, Wen C, Whalen S, Willsey A, Wong W, Wu H, Wu F, Wuchty S, Wylie D, Yap C, Zeng B, Zhang P, Zhang C, Zhang B, Zhang Y, Ziffra R, Zeier Z, Zintel T. Single-cell genomics and regulatory networks for 388 human brains. Science 2024, 384: eadi5199. PMID: 38781369, PMCID: PMC11365579, DOI: 10.1126/science.adi5199.Peer-Reviewed Original ResearchConceptsSingle-cell genomicsSingle-cell expression quantitative trait locusExpression quantitative trait lociDrug targetsQuantitative trait lociPopulation-level variationSingle-cell expressionCell typesDisease-risk genesTrait lociGene familyRegulatory networksGene expressionCell-typeMultiomics datasetsSingle-nucleiGenomeGenesCellular changesHeterogeneous tissuesExpressionCellsChromatinLociMultiomics
2022
Positive modulation of N-methyl-D-aspartate receptors in the mPFC reduces the spontaneous recovery of fear
Lee B, Pothula S, Wu M, Kang H, Girgenti MJ, Picciotto MR, DiLeone RJ, Taylor JR, Duman RS. Positive modulation of N-methyl-D-aspartate receptors in the mPFC reduces the spontaneous recovery of fear. Molecular Psychiatry 2022, 27: 2580-2589. PMID: 35418600, PMCID: PMC9135632, DOI: 10.1038/s41380-022-01498-7.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsExtinction, PsychologicalFearMaleMicePrefrontal CortexRatsRats, Sprague-DawleyReceptors, N-Methyl-D-AspartateConceptsPosttraumatic stress disorderFear extinctionInfralimbic medial prefrontal cortexFear conditioning modelEnhanced fear extinctionFear-based behaviorsProlonged stress modelMedial prefrontal cortexSpontaneous recoveryIL-mPFCPTSD modelPTSD treatmentStress disorderPrefrontal cortexSPS modelN-methyl-D-aspartate receptor modulatorsBrain-derived neurotrophic factorN-methyl-D-aspartate receptorsBehavioral effectsIncreased attentionMPFCPreclinical findingsPyramidal neuronsNeurotrophic factorMale mice
2020
Cortical Transcriptomic Alterations in Association With Appetitive Neuropeptides and Body Mass Index in Posttraumatic Stress Disorder
Stone LA, Girgenti MJ, Wang J, Ji D, Zhao H, Krystal JH, Duman R. Cortical Transcriptomic Alterations in Association With Appetitive Neuropeptides and Body Mass Index in Posttraumatic Stress Disorder. The International Journal Of Neuropsychopharmacology 2020, 24: 118-129. PMID: 32951025, PMCID: PMC8611677, DOI: 10.1093/ijnp/pyaa072.Peer-Reviewed Original ResearchConceptsUpstream regulatorGene co-expression network analysisCo-expression network analysisFunctional genomic studiesPutative upstream regulatorsIngenuity Pathway Analysis softwarePathway Analysis softwarePathway annotationGenomic studiesTranscriptomic modulesTranscriptomic dataTranscriptomic alterationsGene expression
2019
Prefrontal cortex interneurons display dynamic sex-specific stress-induced transcriptomes
Girgenti MJ, Wohleb ES, Mehta S, Ghosal S, Fogaca MV, Duman RS. Prefrontal cortex interneurons display dynamic sex-specific stress-induced transcriptomes. Translational Psychiatry 2019, 9: 292. PMID: 31712551, PMCID: PMC6848179, DOI: 10.1038/s41398-019-0642-z.Peer-Reviewed Original ResearchConceptsFluorescence-activated cell sortingInitiation factor 2Distinct transcriptome profilesTranslational machineryTranscriptome profilesEnriched pathwaysTranscriptional pathwaysTranscriptional profilesRNA sequencingDepressive-like behaviorSST interneuronsKey pathwaysChronic stressInterneuron subtypesSex-specific differencesPrefrontal cortexCell sortingSignificant dysregulationFactor 2PathwayStress-induced depressive-like behaviorDecreased expressionReporter miceGrowth factorNon-stressed femalesKetamine 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 neurotransmission
2016
Ketamine accelerates fear extinction via mTORC1 signaling
Girgenti MJ, Ghosal S, LoPresto D, Taylor JR, Duman RS. Ketamine accelerates fear extinction via mTORC1 signaling. Neurobiology Of Disease 2016, 100: 1-8. PMID: 28043916, PMCID: PMC5907920, DOI: 10.1016/j.nbd.2016.12.026.Peer-Reviewed Original ResearchConceptsPost-traumatic stress disorderMedial prefrontal cortexTreatment of PTSDFear conditioningRetrieval of extinctionExpression of extinctionActivity-dependent effectsTraumatic memoriesStress disorderExtinction exposurePTSD patientsPrefrontal cortexEffects of ketamineGlutamate NMDA receptor antagonistSymptom severityConditioningInfusion of ketamineExtinctionCuesRodent modelsMemoryKetamine administrationReceptor antagonistPresent studyNMDA receptor antagonist