Featured Publications
Astrocytes and microglia play orchestrated roles and respect phagocytic territories during neuronal corpse removal in vivo
Damisah EC, Hill RA, Rai A, Chen F, Rothlin CV, Ghosh S, Grutzendler J. Astrocytes and microglia play orchestrated roles and respect phagocytic territories during neuronal corpse removal in vivo. Science Advances 2020, 6: eaba3239. PMID: 32637606, PMCID: PMC7319765, DOI: 10.1126/sciadv.aba3239.Peer-Reviewed Original ResearchConceptsCorpse removalPrecise spatiotemporal resolutionApoptotic cell removalReceptor tyrosine kinasesGlial cellsOrchestrated rolesTyrosine kinaseApoptotic bodiesCell deathSpecialized roleCoordinated interactionPhagocytic interactionSingle cellsBrain homeostasisCellsCell removalIntravital optical imagingSpatiotemporal resolutionRole of phagocytesSynchronized fashionKinaseMarked delayRoleHomeostasisAstrocytesMicroglia-Mediated Neuroprotection, TREM2, and Alzheimer’s Disease: Evidence From Optical Imaging
Condello C, Yuan P, Grutzendler J. Microglia-Mediated Neuroprotection, TREM2, and Alzheimer’s Disease: Evidence From Optical Imaging. Biological Psychiatry 2017, 83: 377-387. PMID: 29169609, PMCID: PMC5767550, DOI: 10.1016/j.biopsych.2017.10.007.Peer-Reviewed Original ResearchConceptsAlzheimer's diseasePlaque compactionAmyloid depositsInvolvement of microgliaPlaque-associated microgliaLate-onset Alzheimer's diseaseMyeloid cells 2Onset Alzheimer's diseaseMicroglia receptorMicroglia polarizationAD neuropathologyAxonal pathologyNeuroprotective functionDisease progressionOptical imaging studiesCurrent evidenceAD riskMicrogliaTherapeutic targetingAdjacent axonsImaging studiesCells 2DiseasePrecise mechanismRecent genetic studiesTREM2 Haplodeficiency in Mice and Humans Impairs the Microglia Barrier Function Leading to Decreased Amyloid Compaction and Severe Axonal Dystrophy
Yuan P, Condello C, Keene CD, Wang Y, Bird TD, Paul SM, Luo W, Colonna M, Baddeley D, Grutzendler J. TREM2 Haplodeficiency in Mice and Humans Impairs the Microglia Barrier Function Leading to Decreased Amyloid Compaction and Severe Axonal Dystrophy. Neuron 2016, 90: 724-739. PMID: 27196974, PMCID: PMC4898967, DOI: 10.1016/j.neuron.2016.05.003.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseAxonal dystrophyAmyloid depositsAD-like miceHuman AD tissueLate-onset Alzheimer's diseaseNovel therapeutic strategiesTREM2 deficiencyTau hyperphosphorylationAD tissueMicroglia processesPharmacological modulationCompact plaquesTherapeutic strategiesHigh-resolution confocalTREM2 mutationsTREM2Barrier functionMiceGreater surface exposureAmyloid fibrilsHaplodeficiencyPlaquesDiseaseDystrophyATP mediates rapid microglial response to local brain injury in vivo
Davalos D, Grutzendler J, Yang G, Kim JV, Zuo Y, Jung S, Littman DR, Dustin ML, Gan WB. ATP mediates rapid microglial response to local brain injury in vivo. Nature Neuroscience 2005, 8: 752-758. PMID: 15895084, DOI: 10.1038/nn1472.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsApyraseAstrocytesBrainBrain InjuriesCell CommunicationChemotaxisConnexinsGliosisGreen Fluorescent ProteinsMiceMice, TransgenicMicrogliaPhagocytosisPurinergic P2 Receptor AntagonistsReaction TimeReceptors, Purinergic P2Receptors, Purinergic P2Y1Signal TransductionConceptsRapid microglial responseMicroglial processesMicroglial responseBrain injuryG protein-coupled purinergic receptorsLocal brain injuryTraumatic brain injurySite of injuryPrincipal immune cellsPresence of apyraseParenchymal microgliaImmune cellsLocal injectionPurinergic receptorsBaseline motilityIntact brainTwo-photon imagingChannel inhibitorsMouse cortexInjuryExtracellular ATPMicrogliaEnzyme apyraseAstrocytesChemotactic responseMicroglia constitute a barrier that prevents neurotoxic protofibrillar Aβ42 hotspots around plaques
Condello C, Yuan P, Schain A, Grutzendler J. Microglia constitute a barrier that prevents neurotoxic protofibrillar Aβ42 hotspots around plaques. Nature Communications 2015, 6: 6176. PMID: 25630253, PMCID: PMC4311408, DOI: 10.1038/ncomms7176.Peer-Reviewed Original ResearchAngiophagy Prevents Early Embolus Washout But Recanalizes Microvessels Through Embolus Extravasation
Grutzendler J, Murikinati S, Hiner B, Ji L, Lam CK, Yoo T, Gupta S, Hafler BP, Adelman RA, Yuan P, Rodriguez G. Angiophagy Prevents Early Embolus Washout But Recanalizes Microvessels Through Embolus Extravasation. Science Translational Medicine 2014, 6: 226ra31. PMID: 24598589, DOI: 10.1126/scitranslmed.3006585.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainCerebrovascular CirculationCoronary CirculationEmbolismFibrinFibrinolysisFundus OculiGreen Fluorescent ProteinsHemodynamicsHumansKidney TubulesLungMacrophagesMiceMice, TransgenicMicrocirculationMicrogliaMicroscopy, Electron, TransmissionMicrovesselsMonocytesPhagocytosisRetinaRetinal VesselsThrombosisConceptsBlood flow reestablishmentHours of occlusionVascular occlusive disordersDifferent therapeutic strategiesEmbolic occlusionOcclusive disordersVessel recanalizationAlveolar spaceTherapeutic strategiesTherapeutic targetHemodynamic pressureFibrinolytic systemPerivascular spacesEmboliRenal tubulesBlood clotsMicrovascular wallMost human organsOcclusionLungExtravasationKidneyEndotheliumMicrovasculatureWashout
2020
TREM2: Modulator of Lipid Metabolism in Microglia
Damisah EC, Rai A, Grutzendler J. TREM2: Modulator of Lipid Metabolism in Microglia. Neuron 2020, 105: 759-761. PMID: 32135085, DOI: 10.1016/j.neuron.2020.02.008.Peer-Reviewed Original ResearchEmerging technologies to study glial cells
Hirbec H, Déglon N, Foo LC, Goshen I, Grutzendler J, Hangen E, Kreisel T, Linck N, Muffat J, Regio S, Rion S, Escartin C. Emerging technologies to study glial cells. Glia 2020, 68: 1692-1728. PMID: 31958188, DOI: 10.1002/glia.23780.Peer-Reviewed Original ResearchConceptsCell typesChallenging biological questionsGlial cellsSpecific cell typesDifferent glial cell typesGlial cell typesBiological questionsPhysiological functionsPrecursor cellsTight interactionOligodendrocyte precursor cellsCellsExperimental approachRelative contributionBrain functionFull understandingSpecific brain functionsRoleFunctionInteractionDevelopmentTranslation
2016
TREM2-mediated early microglial response limits diffusion and toxicity of amyloid plaques
Wang Y, Ulland TK, Ulrich JD, Song W, Tzaferis JA, Hole JT, Yuan P, Mahan TE, Shi Y, Gilfillan S, Cella M, Grutzendler J, DeMattos RB, Cirrito JR, Holtzman DM, Colonna M. TREM2-mediated early microglial response limits diffusion and toxicity of amyloid plaques. Journal Of Experimental Medicine 2016, 213: 667-675. PMID: 27091843, PMCID: PMC4854736, DOI: 10.1084/jem.20151948.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseTREM2 deficiencyAβ accumulationNeuritic damageAβ plaquesMyeloid cellsAbsence of TREM2Impact of TREM2Rare TREM2 variantsAmyloid β accumulationBrain-resident microgliaMyeloid cells 2Peripheral blood monocytesEarly time pointsMicroglial clusteringMicroglial receptorΒ accumulationAβ depositsNeuronal degenerationTREM2 variantsAmyloid plaquesMurine modelBlood monocytesMatter of debateMicroglia
2010
CX3CR1 in Microglia Regulates Brain Amyloid Deposition through Selective Protofibrillar Amyloid-β Phagocytosis
Liu Z, Condello C, Schain A, Harb R, Grutzendler J. CX3CR1 in Microglia Regulates Brain Amyloid Deposition through Selective Protofibrillar Amyloid-β Phagocytosis. Journal Of Neuroscience 2010, 30: 17091-17101. PMID: 21159979, PMCID: PMC3077120, DOI: 10.1523/jneurosci.4403-10.2010.Peer-Reviewed Original ResearchConceptsCX3CR1-deficient miceAlzheimer's diseaseAmyloid-β PhagocytosisBrain amyloid depositionLower brain levelsGreater phagocytic capacityQuantification of AβHigh proliferative rateAβ phagocytosisActivated microgliaMicroglia activationMicroglia activityAmyloid pathologyAmyloid depositionMicroglia densityBrain levelsPlaque depositionSynaptic damageChemokine receptorsDisease progressionMicrogliaTherapeutic strategiesAmyloid depositsPhagocytic capacityPhagocytic ability