2025
Microglia modulate the cerebrovascular reactivity through ectonucleotidase CD39
Fu Z, Ganesana M, Hwang P, Tan X, Kinkaid M, Sun Y, Bian E, Weybright A, Chen H, Sol-Church K, Eyo U, Pridans C, Quintana F, Robson S, Kumar P, Venton B, Schaefer A, Kuan C. Microglia modulate the cerebrovascular reactivity through ectonucleotidase CD39. Nature Communications 2025, 16: 956. PMID: 39843911, PMCID: PMC11754601, DOI: 10.1038/s41467-025-56093-5.Peer-Reviewed Original ResearchConceptsCerebral blood flowEctonucleotidases CD39Whisker stimulationResponse to whisker stimulationCerebrovascular reactivityDeletion of CD39Blood flowInjection of adenosine triphosphateModulation of cerebral blood flowRegulation of cerebral blood flowExtracellular adenosine triphosphateInjection of adenosineBorder-associated macrophagesMicroglia repopulationExtracellular adenosineAdenosine triphosphateFemale miceBlood flow anomaliesP2RY12 receptorCo-transmitterMouse modelPharmacological inhibitionCD39MicrogliaMice
2024
Olfactory Development and Dysfunction: Involvement of Microglia
Meller S, Greer C. Olfactory Development and Dysfunction: Involvement of Microglia. Physiology 2024, 40: 174-184. PMID: 39499248, DOI: 10.1152/physiol.00037.2024.Peer-Reviewed Original ResearchInvolvement of microgliaPotential involvement of microgliaOlfactory developmentImmune responseOlfactory deficitsEnvironmental insultsResponse to environmental insultsMicroglia-mediated immune responseOlfactory lossOlfactory systemPeriod of neurogenesisNeuronal migrationPotential involvementMicrogliaDiseaseViral diseasesInsultOlfactoryDeficitsBrain energy metabolism: A roadmap for future research
Rae C, Baur J, Borges K, Dienel G, Díaz‐García C, Douglass S, Drew K, Duarte J, Duran J, Kann O, Kristian T, Lee‐Liu D, Lindquist B, McNay E, Robinson M, Rothman D, Rowlands B, Ryan T, Scafidi J, Scafidi S, Shuttleworth C, Swanson R, Uruk G, Vardjan N, Zorec R, McKenna M. Brain energy metabolism: A roadmap for future research. Journal Of Neurochemistry 2024, 168: 910-954. PMID: 38183680, PMCID: PMC11102343, DOI: 10.1111/jnc.16032.Peer-Reviewed Original Research
2023
Microglia in Central Control of Metabolism
Kim J, Copperi F, Diano S. Microglia in Central Control of Metabolism. Physiology 2023, 39: 5-17. PMID: 37962895, PMCID: PMC11283896, DOI: 10.1152/physiol.00021.2023.Peer-Reviewed Original ResearchNicotinic regulation of microglia: potential contributions to addiction
Soares A, Picciotto M. Nicotinic regulation of microglia: potential contributions to addiction. Journal Of Neural Transmission 2023, 131: 425-435. PMID: 37778006, PMCID: PMC11189589, DOI: 10.1007/s00702-023-02703-9.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsNeuroimmune signalingNicotine addictionΑ7 nicotinic acetylcholine receptorAnti-inflammatory cascadeAnti-inflammatory effectsEffects of nicotineAnti-inflammatory compoundsIntracellular calcium concentrationNicotinic acetylcholine receptorsMicroglial polarizationNicotinic regulationMicroglial activityMicroglial signalingImmunomodulatory effectsImmunosuppressive effectsWithdrawal symptomsCytokine releaseCircuit disruptionPreclinical literaturePreclinical studiesΑ7 nAChRsCircuit dysregulationNicotine dependenceMicrogliaAcetylcholine receptorsThe VCAM1–ApoE pathway directs microglial chemotaxis and alleviates Alzheimer’s disease pathology
Lau S, Wu W, Wong H, Ouyang L, Qiao Y, Xu J, Lau J, Wong C, Jiang Y, Holtzman D, Fu A, Ip N. The VCAM1–ApoE pathway directs microglial chemotaxis and alleviates Alzheimer’s disease pathology. Nature Aging 2023, 3: 1219-1236. PMID: 37735240, PMCID: PMC10570140, DOI: 10.1038/s43587-023-00491-1.Peer-Reviewed Original ResearchConceptsDanger-associated molecular patternsAlzheimer's diseaseMicroglial chemotaxisAmeliorate AD pathologyDisease pathologyAlzheimer's disease pathologyAmyloid-betaFunctional screeningPlaque-associatedMicroglial clearanceAD pathologyExtrinsic signalsPhagocytic clearanceExacerbate disease pathologyMolecular patternsIL-33ChemotaxisMicroglial functionAlzheimerVCAM1Interleukin-33Higher cerebrospinal fluid levelsApoPathwayMicrogliaThe brain's polymath: Emerging roles of microglia throughout brain development
Wong F, Favuzzi E. The brain's polymath: Emerging roles of microglia throughout brain development. Current Opinion In Neurobiology 2023, 79: 102700. PMID: 36848726, DOI: 10.1016/j.conb.2023.102700.Peer-Reviewed Original ResearchConceptsPotential contribution of microgliaResident brain immune cellsInfluence neuronal connectivityBrain immune cellsDevelopment of functional networksContribution of microgliaNeuronal circuit developmentElements of neural circuitsImmune cellsNeuronal activityExtracellular matrixSynapse pruningNeuron numberPrune synapsesMicrogliaBrain developmentNeuronal connectivityNeural circuitsBrain wiringCircuit developmentFunctional networksBrainIntegrative viewCircuit wiringIncreased understanding
2022
Interferon opens up: HIV-induced inflammation reconfigures 3D chromatin conformation and affects where HIV integrates
Wei Y, Ho Y. Interferon opens up: HIV-induced inflammation reconfigures 3D chromatin conformation and affects where HIV integrates. Molecular Cell 2022, 82: 4585-4587. PMID: 36525953, PMCID: PMC9925257, DOI: 10.1016/j.molcel.2022.11.013.Peer-Reviewed Original ResearchAdvanced in vitro models: Microglia in action
Cakir B, Kiral F, Park I. Advanced in vitro models: Microglia in action. Neuron 2022, 110: 3444-3457. PMID: 36327894, DOI: 10.1016/j.neuron.2022.10.004.Peer-Reviewed Original ResearchSingle cell spatial analysis reveals the topology of immunomodulatory purinergic signaling in glioblastoma
Coy S, Wang S, Stopka S, Lin J, Yapp C, Ritch C, Salhi L, Baker G, Rashid R, Baquer G, Regan M, Khadka P, Cole K, Hwang J, Wen P, Bandopadhayay P, Santi M, De Raedt T, Ligon K, Agar N, Sorger P, Touat M, Santagata S. Single cell spatial analysis reveals the topology of immunomodulatory purinergic signaling in glioblastoma. Nature Communications 2022, 13: 4814. PMID: 35973991, PMCID: PMC9381513, DOI: 10.1038/s41467-022-32430-w.Peer-Reviewed Original ResearchConceptsPediatric high-grade gliomasHigh-grade gliomasDiffuse midline gliomaH3K27M-mutant diffuse midline gliomaAstrocyte-like differentiationPoor outcomeInflammatory microenvironmentClinical significanceMidline gliomaTherapeutic targetingMyeloid cellsPurinergic signalingImmune adaptationEGFR amplificationTumor cellsGliomasExtracellular purinergicPurinergicGlioblastomaCD39CD73Functional stateMicroenvironmentMicrogliaCellsMicroglia contribute to the postnatal development of cortical somatostatin-positive inhibitory cells and to whisker-evoked cortical activity
Gesuita L, Cavaccini A, Argunsah A, Favuzzi E, Ibrahim L, Stachniak T, De Gennaro M, Utz S, Greter M, Karayannis T. Microglia contribute to the postnatal development of cortical somatostatin-positive inhibitory cells and to whisker-evoked cortical activity. Cell Reports 2022, 40: 111209. PMID: 35977514, PMCID: PMC9396528, DOI: 10.1016/j.celrep.2022.111209.Peer-Reviewed Original ResearchHuman Down syndrome microglia are up for a synaptic feast
Kiral FR, Park IH. Human Down syndrome microglia are up for a synaptic feast. Cell Stem Cell 2022, 29: 1007-1008. PMID: 35803219, DOI: 10.1016/j.stem.2022.06.008.Peer-Reviewed Original ResearchGetting the right cells
Cakir B, Park IH. Getting the right cells. ELife 2022, 11: e80373. PMID: 35770899, PMCID: PMC9246363, DOI: 10.7554/elife.80373.Peer-Reviewed Original ResearchThe immunology of Parkinson’s disease
Zhu B, Yin D, Zhao H, Zhang L. The immunology of Parkinson’s disease. Seminars In Immunopathology 2022, 44: 659-672. PMID: 35674826, PMCID: PMC9519672, DOI: 10.1007/s00281-022-00947-3.Peer-Reviewed Original ResearchConceptsAdaptive immune responsesImmune responseParkinson's diseaseT cellsGut-brain axis hypothesisOnset of PDΑ-synucleinGastro-intestinal symptomsCommon neurodegenerative disorderInnate immune responseΑ-synuclein aggregationPD patientsDopaminergic neuronsLewy bodiesSubstantia nigraNeuronal deathDisease progressionNeuropathological hallmarksProdromal phaseCurrent treatmentNeurodegenerative disordersDiseaseBrainMicrogliaPatients
2021
Microglia regulate brain Progranulin levels through the endocytosis-lysosomal pathway
Dong T, Tejwani L, Jung Y, Kokubu H, Luttik K, Driessen TM, Lim J. Microglia regulate brain Progranulin levels through the endocytosis-lysosomal pathway. JCI Insight 2021, 6: e136147. PMID: 34618685, PMCID: PMC8663778, DOI: 10.1172/jci.insight.136147.Peer-Reviewed Original ResearchConceptsPGRN levelsNovel potential therapeutic targetFrontotemporal lobar degenerationPotential therapeutic targetNeuronal ceroid lipofuscinosisPGRN deficiencyPGRN expressionLysosomal pathwayProgranulin levelsPathological changesHaploinsufficient miceTherapeutic targetMicrogliaNeuropathological phenotypeAlzheimer's diseaseProgranulinCeroid lipofuscinosisGlycoprotein progranulinNeurodegenerative diseasesDiseaseMiceGenetic alterationsNemo-like kinaseGenetic interaction studiesGenetic variantsMicroglial Phenotypic Transition: Signaling Pathways and Influencing Modulators Involved in Regulation in Central Nervous System Diseases
Li J, Shui X, Sun R, Wan L, Zhang B, Xiao B, Luo Z. Microglial Phenotypic Transition: Signaling Pathways and Influencing Modulators Involved in Regulation in Central Nervous System Diseases. Frontiers In Cellular Neuroscience 2021, 15: 736310. PMID: 34594188, PMCID: PMC8476879, DOI: 10.3389/fncel.2021.736310.Peer-Reviewed Original ResearchPhenotypic transitionSignaling pathwayCentral nervous systemInnate immune systemCentral nervous system developmentMolecular insightsPotential therapeutic targetCentral nervous system diseasesAnti-inflammatory phenotypeAssociated with neuronsNervous system diseasesTherapeutic targetSystemic diseasePro-inflammatoryInfluence modulationImmune systemPathwayNervous systemLesion occurrenceMicrogliaPhenotypeNormal conditionsSignalGABA-receptive microglia selectively sculpt developing inhibitory circuits
Favuzzi E, Huang S, Saldi G, Binan L, Ibrahim L, Fernández-Otero M, Cao Y, Zeine A, Sefah A, Zheng K, Xu Q, Khlestova E, Farhi S, Bonneau R, Datta S, Stevens B, Fishell G. GABA-receptive microglia selectively sculpt developing inhibitory circuits. Cell 2021, 184: 4048-4063.e32. PMID: 34233165, PMCID: PMC9122259, DOI: 10.1016/j.cell.2021.06.018.Peer-Reviewed Original ResearchConceptsInhibitory cortical synapsesBrain wiringResident immune cellsMouse postnatal developmentBehavioral abnormalitiesImmune cellsInhibitory circuitsSynaptic refinementGlial cell typesExcitatory synapsesCortical synapsesPostnatal developmentMicrogliaSynapse typesInhibitory connectionsCell typesBrainRemodeling programSynapsesAbnormalitiesGABAUcp2-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 speciesSoluble α-synuclein–antibody complexes activate the NLRP3 inflammasome in hiPSC-derived microglia
Trudler D, Nazor K, Eisele Y, Grabauskas T, Dolatabadi N, Parker J, Sultan A, Zhong Z, Goodwin M, Levites Y, Golde T, Kelly J, Sierks M, Schork N, Karin M, Ambasudhan R, Lipton S. Soluble α-synuclein–antibody complexes activate the NLRP3 inflammasome in hiPSC-derived microglia. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2025847118. PMID: 33833060, PMCID: PMC8054017, DOI: 10.1073/pnas.2025847118.Peer-Reviewed Original ResearchConceptsHuman microgliaLike receptor family pyrinFibrillar αSynA9 dopaminergic neuronsInterleukin-1β secretionCaspase-1 activationMicroglial activationFamily pyrinAntibody therapyNeuronal deathParkinson's diseaseMicrogliaMouse brainΑ-synucleinDual stimulationMitochondrial damageΑSynAntibodiesInflammationNLRP3Cognate antibodiesHuman brainDiseaseNeuronsStem cells
2020
Genomics Links Inflammation With Neurocognitive Impairment in Children Living With Human Immunodeficiency Virus Type-1
Rawat P, Brummel S, Singh K, Kim J, Frazer K, Nichols S, Seage G, Williams P, Van Dyke R, Harismendy O, Trout R, Spector S. Genomics Links Inflammation With Neurocognitive Impairment in Children Living With Human Immunodeficiency Virus Type-1. The Journal Of Infectious Diseases 2020, 224: 870-880. PMID: 33373444, PMCID: PMC8408770, DOI: 10.1093/infdis/jiaa792.Peer-Reviewed Original ResearchMeSH Keywords14-3-3 ProteinsChildChild, PreschoolFemaleGenome-Wide Association StudyGenomicsHIV InfectionsHIV-1HumansInfantInfectious Disease Transmission, VerticalInflammasomesInflammationIntracellular Signaling Peptides and ProteinsMaleMembrane ProteinsMicrogliaNeurocognitive DisordersReceptors, CCRConceptsWhole-exome sequencingValidation cohortNeurocognitive impairmentOdds ratioRisk of NCIHuman immunodeficiency virus type 1Immunodeficiency virus type 1Single nucleotide variantsAdjusted odds ratioIL-1β releaseVirus type 1Microglial releaseIL-1βHuman microgliaDecreased oddsType 1Logistic regressionCognitive scoresCCRL2MicrogliaFurther studiesHIVInflammationCsACohort
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