2025
Mitofusin 2 controls mitochondrial and synaptic dynamics of suprachiasmatic VIP neurons and related circadian rhythms
Stoiljkovic M, Song J, Hong H, Endle H, Varela L, Catarino J, Gao X, Liu Z, Sotonyi P, Diano S, Cedernaes J, Bass J, Horvath T. Mitofusin 2 controls mitochondrial and synaptic dynamics of suprachiasmatic VIP neurons and related circadian rhythms. Journal Of Clinical Investigation 2025, 135: e185000. PMID: 40590229, PMCID: PMC12208536, DOI: 10.1172/jci185000.Peer-Reviewed Original ResearchConceptsMitochondrial dynamicsMitofusin 2Perturb mitochondrial dynamicsDaily biological rhythmsEnvironmental cuesCellular adaptationMammalian organismsCircadian oscillatorVIP neuronsConditional ablationMitochondriaLD cycleCircadian rhythmicityLight/darkAdvanced phase angleCircadian rhythmSynaptic input organizationMitofusinBiological rhythmsMfn2OrganizationInput organizationNeuronsCore body temperatureSynaptic dynamics
2024
Kisspeptin signaling in astrocytes modulates the reproductive axis
Torres E, Pellegrino G, Granados-Rodríguez M, Fuentes-Fayos A, Velasco I, Coutteau-Robles A, Legrand A, Shanabrough M, Perdices-Lopez C, Leon S, Yeo S, Manchishi S, Sánchez-Tapia M, Navarro V, Pineda R, Roa J, Naftolin F, Argente J, Luque R, Chowen J, Horvath T, Prevot V, Sharif A, Colledge W, Tena-Sempere M, Romero-Ruiz A. Kisspeptin signaling in astrocytes modulates the reproductive axis. Journal Of Clinical Investigation 2024, 134: e172908. PMID: 38861336, PMCID: PMC11291270, DOI: 10.1172/jci172908.Peer-Reviewed Original ResearchResponse to metabolic stressProtein-protein interactionsMetabolic stressOntology analysisReproductive axisKisspeptin signalingGene expressionKisspeptin actionHypothalamic GnRH neuronsProteomic profilingFemale pubertal onsetReproductive modulesExpression of KISS1RLH secretory profilesSignaling-pathwayCellular co-expressionConditional ablationResponse to kisspeptinLH responses to kisspeptinNon-neuronal pathwaysAstrocytes in vivoHigh-fat dietGFAP-positive cellsPathwayReproductive controlMacrophage-derived macrophage migration inhibitory factor mediates renal injury in anti-glomerular basement membrane glomerulonephritis
Yang H, Li J, Huang X, Bucala R, Xu A, Lan H. Macrophage-derived macrophage migration inhibitory factor mediates renal injury in anti-glomerular basement membrane glomerulonephritis. Frontiers In Immunology 2024, 15: 1361343. PMID: 38846956, PMCID: PMC11153660, DOI: 10.3389/fimmu.2024.1361343.Peer-Reviewed Original ResearchMacrophage migration inhibitory factorMigration inhibitory factorTreatment of immune-mediated kidney diseasesMacrophage MIFMIF depletionPathogenic roleSource of MIFImmune-mediated kidney diseasesAnti-glomerular basement membrane glomerulonephritisInhibitory factorT cell recruitmentGlomerular crescent formationTh17 immune responsesReduced serum creatininePolarization of macrophagesRenal macrophagesSerum creatinineCrescentic glomerulonephritisInhibiting Th1Renal injuryControl miceCreatine clearanceCrescent formationMembranous glomerulonephritisConditional ablation
2023
Innate immune cell-intrinsic ketogenesis is dispensable for organismal metabolism and age-related inflammation
Goldberg E, Letian A, Dlugos T, Leveau C, Dixit V. Innate immune cell-intrinsic ketogenesis is dispensable for organismal metabolism and age-related inflammation. Journal Of Biological Chemistry 2023, 299: 103005. PMID: 36775129, PMCID: PMC10025153, DOI: 10.1016/j.jbc.2023.103005.Peer-Reviewed Original ResearchConceptsAge-related inflammationKetone bodiesOrganismal metabolismMyeloid cellsChronic low-grade inflammationKetogenic diet feedingLow-grade inflammationHigh-fat dietAbundant ketone bodyGlucose toleranceNLRP3 inflammasomeDiet feedingGlucose homeostasisMouse modelBody weightInflammationMetabolic checkpointOnly organConditional ablationTerminal enzymeΒ-hydroxybutyrateFunctional targetingMethylglutaryl-CoA lyaseKetogenesisModest effect
2021
Elevated murine HB-EGF confers sensitivity to diphtheria toxin in EGFR-mutant lung adenocarcinoma
Robles-Oteiza C, Ayeni D, Levy S, Homer RJ, Kaech SM, Politi K. Elevated murine HB-EGF confers sensitivity to diphtheria toxin in EGFR-mutant lung adenocarcinoma. Disease Models & Mechanisms 2021, 14: dmm049072. PMID: 34494649, PMCID: PMC8617309, DOI: 10.1242/dmm.049072.Peer-Reviewed Original ResearchConceptsHuman diphtheria toxin receptorDiphtheria toxin receptorTumor regressionEGFR-mutant lung cancerEGFR-mutant lung adenocarcinomaEGFR-mutant tumorsMutant EGFRTissue-specific promotorsFVB miceLung cancerSystemic administrationLung adenocarcinomaMurine lungRapid regressionConditional ablationTumor cellsUpregulated expressionMiceElevated expressionToxin receptorHB-EGFCell populationsHBEGFEGFRPrimary targetUcp2-dependent microglia-neuronal coupling controls ventral hippocampal circuit function and anxiety-like behavior
Yasumoto Y, Stoiljkovic M, Kim JD, Sestan-Pesa M, Gao XB, Diano S, Horvath TL. Ucp2-dependent microglia-neuronal coupling controls ventral hippocampal circuit function and anxiety-like behavior. Molecular Psychiatry 2021, 26: 2740-2752. PMID: 33879866, PMCID: PMC8056795, DOI: 10.1038/s41380-021-01105-1.Peer-Reviewed Original ResearchConceptsAnxiety-like behaviorReactive oxygen speciesMicroglia-synapse contactsSpine synapse numberHippocampal circuit functionNeuronal circuit dysfunctionMicroglial productionVentral hippocampusCircuit dysfunctionSpine synapsesSynapse numberAdult brainTransient riseMitochondrial ROS generationMicrogliaBrain functionConditional ablationPhagocytic inclusionsSynaptic elementsProtein 2ROS generationSignificant reductionCircuit functionConsequent accumulationOxygen species
2017
The Xenopus tadpole: An in vivo model to screen drugs favoring remyelination
Mannioui A, Vauzanges Q, Fini JB, Henriet E, Sekizar S, Azoyan L, Thomas JL, Du Pasquier D, Giovannangeli C, Demeneix B, Lubetzki C, Zalc B. The Xenopus tadpole: An in vivo model to screen drugs favoring remyelination. Multiple Sclerosis Journal 2017, 24: 1421-1432. PMID: 28752787, DOI: 10.1177/1352458517721355.Peer-Reviewed Original ResearchConceptsSphingosine-1-phosphate receptor 5Receptor 5Sphingosine-1-phosphate receptor 1Efficacy of siponimodNumber of oligodendrocytesSpontaneous remyelinationMultiple sclerosisOptic nervePromyelinating effectE. coli nitroreductaseRemyelinationDual agonistsVivo modelReceptor 1SiponimodConditional ablationOligodendrocytesXenopus tadpolesVivo screeningCRISPR/Cas9 gene editingVivoCas9 gene editingDemyelinationSclerosisGreen fluorescent protein reporter
2013
The Ligand Binding Domain of GCNF Is Not Required for Repression of Pluripotency Genes in Mouse Fetal Ovarian Germ Cells
Okumura LM, Lesch BJ, Page DC. The Ligand Binding Domain of GCNF Is Not Required for Repression of Pluripotency Genes in Mouse Fetal Ovarian Germ Cells. PLOS ONE 2013, 8: e66062. PMID: 23762465, PMCID: PMC3676325, DOI: 10.1371/journal.pone.0066062.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDown-RegulationExonsFemaleFetusGene Expression Regulation, DevelopmentalGene TargetingGerm CellsHomeodomain ProteinsLigandsMeiosisMiceMice, Inbred C57BLMice, Mutant StrainsMutationNanog Homeobox ProteinNuclear Receptor Subfamily 6, Group A, Member 1Octamer Transcription Factor-3OogenesisOvaryPhenotypePluripotent Stem CellsProtein BindingProtein Structure, TertiarySequence DeletionStructure-Activity RelationshipConceptsFetal ovarian germ cellsOvarian germ cellsPluripotency genesSomatic cellsGerm cellsSilencing of Oct4Initiation of meiosisEmbryonic stem cellsLigand binding domainsGCNF geneEmbryonic day 14.5Tamoxifen-inducible CreDifferent developmental timepointsBinding domainsDifferentiated stateGCNFDevelopmental timepointsNanogGenesConditional ablationStem cellsDay 14.5CellsExpressionE8.0
2012
Live Imaging of Targeted Cell Ablation in Xenopus: A New Model to Study Demyelination and Repair
Kaya F, Mannioui A, Chesneau A, Sekizar S, Maillard E, Ballagny C, Houel-Renault L, DuPasquier D, Bronchain O, Holtzmann I, Desmazieres A, Thomas JL, Demeneix BA, Brophy PJ, Zalc B, Mazabraud A. Live Imaging of Targeted Cell Ablation in Xenopus: A New Model to Study Demyelination and Repair. Journal Of Neuroscience 2012, 32: 12885-12895. PMID: 22973012, PMCID: PMC3460536, DOI: 10.1523/jneurosci.2252-12.2012.Peer-Reviewed Original ResearchConceptsDemyelination/remyelination processesProcess of demyelinationAxonal damageRemyelination processMyelin repairOligodendrocyte ablationMTZ treatmentTwo-photon imagingVivo modelTargeted cell ablationMetronidazoleTherapeutic agentsConditional ablationRetinoic acidOligodendrocytesDemyelinationRemyelination
2009
MEKK3 Is Essential for Lymphopenia-Induced T Cell Proliferation and Survival
Wang X, Chang X, Facchinetti V, Zhuang Y, Su B. MEKK3 Is Essential for Lymphopenia-Induced T Cell Proliferation and Survival. The Journal Of Immunology 2009, 182: 3597-3608. PMID: 19265138, PMCID: PMC2923428, DOI: 10.4049/jimmunol.0803738.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell DifferentiationCell ProliferationCell SurvivalCells, CulturedGene Knock-In TechniquesHomeostasisLymphopeniaMAP Kinase Kinase Kinase 3MiceMice, Inbred C57BLMice, KnockoutMice, TransgenicMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Thymus GlandConceptsT cell proliferationT cell homeostasisT cellsCell proliferationPeripheral T cell numbersSelf-peptide MHCTCR stimulationT cell immunityT cell numbersThymic T cell developmentConditional knockout miceCell homeostasisT cell developmentCell immunityActivity of ERK1/2Knockout miceConditional ablationPeptide-MHCP38 MAPKLymphopeniaCell numberSignificant reductionCell developmentSelective roleProliferation
2001
Neurotrophin-3 modulates noradrenergic neuron function and opiate withdrawal
Akbarian S, Bates B, Liu R, Skirboll S, Pejchal T, Coppola V, Sun L, Fan G, Kucera J, Wilson M, Tessarollo L, Kosofsky B, Taylor J, Bothwell M, Nestler E, Aghajanian G, Jaenisch R. Neurotrophin-3 modulates noradrenergic neuron function and opiate withdrawal. Molecular Psychiatry 2001, 6: 593-604. PMID: 11526474, DOI: 10.1038/sj.mp.4000897.Peer-Reviewed Original ResearchMeSH KeywordsAgingAnimalsAvoidance LearningBrainColforsinCyclic AMPElectric StimulationEnkephalin, Ala(2)-MePhe(4)-Gly(5)-Gene Expression Regulation, EnzymologicIn Vitro TechniquesIntermediate Filament ProteinsLocus CoeruleusMiceMice, KnockoutMice, TransgenicMorphineMorphine DependenceNerve Tissue ProteinsNestinNeuronsNeurotrophin 3Signal TransductionSubstance Withdrawal SyndromeTyrosine 3-MonooxygenaseConceptsNoradrenergic neuronsNeurotrophin-3NT-3Opiate withdrawalNoradrenergic signalingOpiate withdrawal symptomsChronic morphine exposureNT-3 expressionNon-catecholaminergic neuronsLoss of neuronsDorsal medullaMorphine exposureWithdrawal symptomsAfferent sourcesTyrosine hydroxylaseAdult brainSomatic symptomsNeuron functionVentral forebrainConditional ablationReduced upregulationNeuronsAltered cAMPSymptomsWithdrawal
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