2025
The role of microglia in multiple sclerosis: implications for treatment with Bruton’s tyrosine kinase inhibitors
Vermersch P, Airas L, Berger T, Deisenhammer F, Grigoriadis N, Hartung H, Magyari M, Popescu V, Pozzilli C, Pugliatti M, Van Wijmeersch B, Zakaria M, Oreja-Guevara C. The role of microglia in multiple sclerosis: implications for treatment with Bruton’s tyrosine kinase inhibitors. Frontiers In Immunology 2025, 16: 1495529. PMID: 40443664, PMCID: PMC12119304, DOI: 10.3389/fimmu.2025.1495529.Peer-Reviewed Original ResearchConceptsBruton tyrosine kinase inhibitorCentral nervous systemTyrosine kinase inhibitorsBruton's tyrosine kinaseMagnetic resonance imagingPositron emission tomographyMultiple sclerosisMicroglial functionPrimary resident immune cellsTissue repairNeural homeostasisPathogenesis of MSPathophysiology of MSResident immune cellsChronic autoimmune diseaseCentral nervous system developmentInvolvement of microgliaPotential therapeutic strategyModulating microglial functionDisease progression rateImmune surveillanceImprove patient outcomesImmune cellsAutoimmune diseasesProgressive MSMicroglial regulation of white matter development and its disruption in autism spectrum disorder
Canada K, Evans T, Pelphrey K. Microglial regulation of white matter development and its disruption in autism spectrum disorder. Cerebral Cortex 2025, 35: bhaf109. PMID: 40302613, DOI: 10.1093/cercor/bhaf109.Peer-Reviewed Original ResearchConceptsAutism spectrum disorderMaternal immune activationWhite matter developmentSpectrum disorderPresentation of autism spectrum disorderService of perceptionCortical brain regionsBrain-resident immune cellsWhite matterResident immune cellsSocial cognitionCore symptomsWhite matter abnormalitiesBrain regionsBrain functionNeurodevelopmental disordersOL lineage cellsImmune dysregulationEfficient neuronal signalingImmune activationImmune cellsCytokine releaseMicroglial reactivityHuman brainLineage cellsMeningeal lymphatics-microglia axis regulates synaptic physiology
Kim K, Abramishvili D, Du S, Papadopoulos Z, Cao J, Herz J, Smirnov I, Thomas J, Colonna M, Kipnis J. Meningeal lymphatics-microglia axis regulates synaptic physiology. Cell 2025, 188: 2705-2719.e23. PMID: 40120575, PMCID: PMC12086007, DOI: 10.1016/j.cell.2025.02.022.Peer-Reviewed Original ResearchConceptsBehavioral alterationsAging-associated cognitive declineMemory taskNeural mechanismsIL-6Cognitive declineIL-6-dependent mechanismInhibitory synaptic inputsCortical circuitryBehavioral changesMeningeal lymphaticsInterleukin-6 geneIL-6 signalingAge-associatedSynaptic inputsLymphatic dysfunctionLymphatic functionCerebrospinal fluidProlonged impairmentIncreased expressionNeurodegenerative conditionsLymphaticsPotential targetDysfunctionDeficitsMicroglial reprogramming: a potential new frontier in enhancing immunotherapy for melanoma brain metastasis
Savion‐Gaiger N, Bar‐Ziv D, Kluger H. Microglial reprogramming: a potential new frontier in enhancing immunotherapy for melanoma brain metastasis. Molecular Oncology 2025, 19: 1291-1294. PMID: 40111148, PMCID: PMC12077281, DOI: 10.1002/1878-0261.70028.Peer-Reviewed Original ResearchConceptsMelanoma brain metastasesBrain metastasesSites of metastatic disseminationHuman brain metastasesAdvanced melanomaEnhance immunotherapyMurine studiesTumor microenvironmentMetastatic disseminationMyeloid cellsMelanoma cellsMelanomaMetastasisMicroglial cellsPotential new frontiersCellsBrainImmunotherapyTumorMicroenvironmentSex differences in the microglial response to stress and chronic alcohol exposure in mice
Soares A, Garcia-Rivas V, Fai C, Thomas M, Zheng X, Picciotto M, Mineur Y. Sex differences in the microglial response to stress and chronic alcohol exposure in mice. Biology Of Sex Differences 2025, 16: 19. PMID: 40038827, PMCID: PMC11881309, DOI: 10.1186/s13293-025-00701-y.Peer-Reviewed Original ResearchConceptsResponse to stressSex differencesAlcohol exposureStress-induced alcohol drinkingHeightened reactivity to stressInescapable footshock stressDevelopment of AUDReactivity to stressChronic alcohol exposureProminent sex differencesIncreased alcohol intakeCharacterize sex differencesFemale C57BL/6J miceDark paradigmComorbid moodFootshock stressStress disorderLimbic circuitsNeurobiological processesModify drinkingNeuroimmune signalingAdministered alcoholFemale rodentsMicroglial densityAlcohol drinkingHIV, smoking, and the brain: a convergence of neurotoxicities
Orlinick B, Farhadian S. HIV, smoking, and the brain: a convergence of neurotoxicities. AIDS Research And Therapy 2025, 22: 13. PMID: 39915881, PMCID: PMC11804093, DOI: 10.1186/s12981-025-00714-y.Peer-Reviewed Original ResearchConceptsHuman immunodeficiency virusCholinergic anti-inflammatory pathwayAnti-inflammatory pathwayNeurocognitive impairmentTobacco smokeEffect of human immunodeficiency virusEffects of tobacco smokingNeurotoxic effectsBrain volume changesClinically significant impactIncreased oxidative stressImmunodeficiency virusAlpha7 nicotinic acetylcholine receptorPWHBrain regionsMicroglial activationCognitive functionBrain healthIncreased neuroinflammationNeuronal apoptosisTherapeutic targetAcetylcholine receptorsGeneral populationNeurotoxicitySmokingCCL21-CCR7 blockade prevents neuroinflammation and degeneration in Parkinson’s disease models
Leser F, Júnyor F, Pagnoncelli I, Delgado A, Medeiros I, Nóbrega A, Andrade B, de Lima M, da Silva N, Jacob L, Boyé K, Geraldo L, de Souza A, Maron-Gutierrez T, Castro-Faria-Neto H, Follmer C, Braga C, Neves G, Eichmann A, Romão L, Lima F. CCL21-CCR7 blockade prevents neuroinflammation and degeneration in Parkinson’s disease models. Journal Of Neuroinflammation 2025, 22: 31. PMID: 39894839, PMCID: PMC11789347, DOI: 10.1186/s12974-024-03318-x.Peer-Reviewed Original ResearchConceptsMouse model of PDModel of PDMouse modelDopaminergic neuronsNeuron-microglia communicationNeuron-glia communicationParkinson's diseaseCCR7-dependent mannerMicroglial cell activationCCR7 expressionCCL21-CCR7Progressive degenerative diseaseCCR7 receptorMicroglial cell migrationInflammatory profileChemokine CCL21Cell activationCCL21Therapeutic strategiesChemokine inhibitorsTherapeutic implicationsMicroglial activationReceptor pathwayCCR7Behavioral deficitsMicroglia 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
Alcohol drinking is attenuated by PDE4 inhibition but partial microglia depletion is not sufficient to block stress-induced escalation of alcohol intake in female mice
Garcia-Rivas V, Soares A, Thomas M, Na J, Smith A, Picciotto M, Mineur Y. Alcohol drinking is attenuated by PDE4 inhibition but partial microglia depletion is not sufficient to block stress-induced escalation of alcohol intake in female mice. Alcohol 2024, 122: 31-42. PMID: 39725336, DOI: 10.1016/j.alcohol.2024.12.004.Peer-Reviewed Original ResearchConceptsAlcohol use disorderEthanol drinkingStress exposureEthanol intakeExposure to foot-shock stressDevelopment of alcohol use disordersTreatment of alcohol use disordersEscalation of alcohol intakeFemale miceReduced ethanol intakeFoot-shock stressIdentified sex differencesInhibitor of phosphodiesterase type 4Alcohol intakeEthanol reinforcementPharmacological depletion of microgliaLimbic circuitsUse disorderChronic ethanolNeuroinflammatory triggerDecreased preferenceC57BL/6J malesPhosphodiesterase type 4Sex differencesBinge drinkingMaresin-1 Ameliorates Sepsis-Induced Microglial Activation Through Modulation of the P38 MAPK Pathway
Dai M, Sun S, Dai Y, Dou X, Yang J, Chen X, Yang D, Lin Y. Maresin-1 Ameliorates Sepsis-Induced Microglial Activation Through Modulation of the P38 MAPK Pathway. Neurochemical Research 2024, 50: 26. PMID: 39565476, DOI: 10.1007/s11064-024-04280-z.Peer-Reviewed Original ResearchConceptsSepsis-induced neuroinflammationM1-type microgliaPro-inflammatory markersPhosphorylation of p38 MAPKP38 MAPK pathwayP38 MAPKDysregulated immune response to infectionMouse cecum ligationImmune response to infectionExpression of pro-inflammatory markersInhibited phosphorylation of p38 MAPKInduce neuronal degenerationMAPK pathwayPuncture (CLP)-induced sepsis modelPotential therapeutic roleP38 MAPK inhibitor SB203580Combination of SB203580Response to infectionMicroglial cell markersLife-threatening diseaseMAPK inhibitor SB203580Co-administrationCell markersCLP modelCecum ligationMicroglia-mediated neuroimmune suppression in PTSD is associated with anhedonia
Bonomi R, Hillmer A, Woodcock E, Bhatt S, Rusowicz A, Angarita G, Carson R, Davis M, Esterlis I, Nabulsi N, Huang Y, Krystal J, Pietrzak R, Cosgrove K. Microglia-mediated neuroimmune suppression in PTSD is associated with anhedonia. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2406005121. PMID: 39172786, PMCID: PMC11363315, DOI: 10.1073/pnas.2406005121.Peer-Reviewed Original ResearchConceptsPTSD groupPrefrontal-limbic circuitsNeuroimmune responseAssociated with anhedoniaPosttraumatic stress disorderPositron emission tomography brain imagingTranslocator protein availabilityBrain immune functionAnhedonic symptomsStress disorderPeripheral immune dysfunctionPTSDGroup differencesSeverity of symptomsPsychiatric diseasesTranslocator proteinBrain imagingAdministration of lipopolysaccharideSymptomsMicroglial markersLPS-induced increaseCompared to controlsImmune functionSickness symptomsAnhedoniaDissecting glial scar formation by spatial point pattern and topological data analysis
Manrique-Castano D, Bhaskar D, ElAli A. Dissecting glial scar formation by spatial point pattern and topological data analysis. Scientific Reports 2024, 14: 19035. PMID: 39152163, PMCID: PMC11329771, DOI: 10.1038/s41598-024-69426-z.Peer-Reviewed Original ResearchSingle-Cell Transcriptomic Analyses of Brain Parenchyma in Patients With New-Onset Refractory Status Epilepticus (NORSE)
Hanin A, Zhang L, Huttner A, Plu I, Mathon B, Bielle F, Navarro V, Hirsch L, Hafler D. Single-Cell Transcriptomic Analyses of Brain Parenchyma in Patients With New-Onset Refractory Status Epilepticus (NORSE). Neurology Neuroimmunology & Neuroinflammation 2024, 11: e200259. PMID: 38810181, PMCID: PMC11139018, DOI: 10.1212/nxi.0000000000200259.Peer-Reviewed Original ResearchConceptsNew-onset refractory status epilepticusTemporal lobe epilepsyGABAergic neuronsExcitatory neuronsInfiltrating macrophagesProportion of GABAergic neuronsChronic temporal lobe epilepsyRefractory status epilepticusInhibitory GABAergic neuronsSingle-cell transcriptome analysisDecreased expression of genesDegree of demyelinationImmune disturbancesNeuronal excitabilityImmune dysregulationNew-onsetStatus epilepticusPoor outcomeRefractory epilepsyHealthy childrenMicroglial reactivitySingle-nucleus RNA sequencingNLRP3 inflammasome activationInflammatory responseLobe epilepsySupervised latent factor modeling isolates cell-type-specific transcriptomic modules that underlie Alzheimer’s disease progression
Hodgson L, Li Y, Iturria-Medina Y, Stratton J, Wolf G, Krishnaswamy S, Bennett D, Bzdok D. Supervised latent factor modeling isolates cell-type-specific transcriptomic modules that underlie Alzheimer’s disease progression. Communications Biology 2024, 7: 591. PMID: 38760483, PMCID: PMC11101463, DOI: 10.1038/s42003-024-06273-8.Peer-Reviewed Original ResearchConceptsGene programAlzheimer's diseaseLate-onset Alzheimer's diseaseAD risk lociCell type-specificSingle-nucleus RNA sequencingRisk lociAD brainAlzheimer's disease progressionSnRNA-seqRNA sequencingAD pathophysiologySignaling cascadesTranscriptome modulationProgressive neurodegenerative diseaseCell-typeGWASNeurodegenerative diseasesNeuronal lossGlial cellsTranscriptomeLociGenesPseudo-trajectoriesDisease progressionBeyond antiviral: role of IFN-I in brain development
Baker C, Iwasaki A. Beyond antiviral: role of IFN-I in brain development. Trends In Immunology 2024, 45: 322-324. PMID: 38644134, DOI: 10.1016/j.it.2024.04.004.Commentaries, Editorials and LettersAbsence in CX3CR1 receptor signaling promotes post‐ischemic stroke cognitive function recovery through suppressed microglial pyroptosis in mice
Ge Y, Yang J, Chen J, Dai M, Dou X, Yao S, Yao C, Lin Y. Absence in CX3CR1 receptor signaling promotes post‐ischemic stroke cognitive function recovery through suppressed microglial pyroptosis in mice. CNS Neuroscience & Therapeutics 2024, 30: e14551. PMID: 38421089, PMCID: PMC10850801, DOI: 10.1111/cns.14551.Peer-Reviewed Original ResearchConceptsMorris water mazeNovel object recognition testObject recognition testCX3CR1<sup>-/-</sup> micePost-stroke cognitive impairmentRecognition testCX3CR1 receptorCognitive behavioral performanceWater mazeBehavioral performanceCognitive dysfunctionDouble-positive cellsCognitive functionSource of morbidityCognitive impairmentPositron emission tomographyEnhanced neurogenesisCognitive function recoveryCX3CR1 knockoutExpression of GSDMDMicroglial pyroptosisChronic phaseInfarct volumeCX3CR1Hippocampus
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 ResearchThe 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 ResearchMeSH KeywordsAlzheimer DiseaseAmyloid beta-PeptidesApolipoproteins EChemotaxisHumansInterleukin-33MicrogliaConceptsDanger-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 levelsApoPathwayMicrogliaReceptor–ligand interaction controls microglial chemotaxis and amelioration of Alzheimer's disease pathology
Lau S, Fu A, Ip N. Receptor–ligand interaction controls microglial chemotaxis and amelioration of Alzheimer's disease pathology. Journal Of Neurochemistry 2023, 166: 891-903. PMID: 37603311, DOI: 10.1111/jnc.15933.Peer-Reviewed Original ResearchConceptsDanger-associated molecular patternsMicroglial chemotaxisAD pathogenesisAlzheimer's diseaseMicroglial functionRepertoire of surface receptorsHyperphosphorylated tauAlzheimer's disease pathologyAmyloid-betaMolecular machineryMicroglial receptorsReceptor-ligand interactionsPhagocytic clearanceReceptor-ligand axisMolecular patternsSurface receptorsFunctional transitionDisease pathologyChemotaxisBrain homeostasisAberrant synaptic pruningClearance activityCritical stepsReceptorsAmyloidLRRK2 suppresses lysosome degradative activity in macrophages and microglia through MiT-TFE transcription factor inhibition
Yadavalli N, Ferguson S. LRRK2 suppresses lysosome degradative activity in macrophages and microglia through MiT-TFE transcription factor inhibition. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2303789120. PMID: 37487100, PMCID: PMC10400961, DOI: 10.1073/pnas.2303789120.Peer-Reviewed Original Research
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