2025
HIV, 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 deficits
2024
Olfactory and trigeminal routes of HSV-1 CNS infection with regional microglial heterogeneity
Niemeyer C, Merle L, Bubak A, Baxter B, Polese A, Colon-Reyes K, Vang S, Hassell J, Bruce K, Nagel M, Restrepo D. Olfactory and trigeminal routes of HSV-1 CNS infection with regional microglial heterogeneity. Journal Of Virology 2024, 98: e00968-24. PMID: 39475273, PMCID: PMC11575344, DOI: 10.1128/jvi.00968-24.Peer-Reviewed Original ResearchCentral nervous systemHerpes simplex virus type 1Trigeminal ganglionVirus type 1Olfactory epitheliumHSV-1Locus coeruleusHSV-1 CNS infectionBrain regionsImmune responseResponse to HSV-1Microglial activationType 1Spread of HSV-1Absence of viral antigenHSV-1 antigenHSV-1 spreadHSV-1 infectionC57BL/6 mouse modelCranial nerve nucleiResponse of macrophagesInflammatory response of macrophagesCNS infectionRaphe nucleusNasal epitheliaGenetic contribution to microglial activation in schizophrenia
Koskuvi M, Pörsti E, Hewitt T, Räsänen N, Wu Y, Trontti K, McQuade A, Kalyanaraman S, Ojansuu I, Vaurio O, Cannon T, Lönnqvist J, Therman S, Suvisaari J, Kaprio J, Blurton-Jones M, Hovatta I, Lähteenvuo M, Rolova T, Lehtonen Š, Tiihonen J, Koistinaho J. Genetic contribution to microglial activation in schizophrenia. Molecular Psychiatry 2024, 29: 2622-2633. PMID: 38519640, PMCID: PMC11420079, DOI: 10.1038/s41380-024-02529-1.Peer-Reviewed Original ResearchIngenuity Pathway AnalysisGene OntologyMajor histocompatibility complexAffected twinHuman induced pluripotent stem cell-derived microgliaExtracellular matrix signalingUpregulation of major histocompatibility complexHealthy individualsIncreased expression of inflammatory genesIncreased expressionMicroglial activationResponse to clozapineStem cell-derived microgliaBrain-resident immune cellsResponse to interleukin-1 betaPathophysiology of schizophreniaInvolvement of neuroinflammatory processesResident immune cellsExpression of inflammatory genesIncreased microglial activationInterleukin-1 betaAberrant activation of microgliaHuman cell modelsRNA sequencingInvading pathogens
2022
2348. Distinct cerebrospinal fluid immune proteins mark neurosyphilis
Catalano A, Yoon J, Farhadian S, Fertuzinhos S, Gisslen M, Zetterberg H, Marra C, Walsh H. 2348. Distinct cerebrospinal fluid immune proteins mark neurosyphilis. Open Forum Infectious Diseases 2022, 9: ofac492.155. DOI: 10.1093/ofid/ofac492.155.Peer-Reviewed Original ResearchHIV statusImmune responseBCA-1/CXCL13Macrophage/microglial activationIP-10/CXCL10IL-8/CXCL8CNS immune responseNeuronal injury markersNon-NS groupPotential CSF biomarkersMIG/CXCL9Date of enrollmentHigh-sensitivity ELISAWilcoxon rank sum testSpecific immune pathwaysMultiple comparisonsRank sum testRace/ethnicityCNS inflammationMicroglial activationCSF WBCElevated markersInjury markersNeuronal damageAsymptomatic diseaseSerum Neurofilament Light Associates with Microglial Activation in the Multiple Sclerosis Brain (S26.010)
Saraste M, Matilainen M, Sucksdorff M, Leppert D, Kuhle J, Airas L. Serum Neurofilament Light Associates with Microglial Activation in the Multiple Sclerosis Brain (S26.010). Neurology 2022, 98 DOI: 10.1212/wnl.98.18_supplement.2588.Peer-Reviewed Original ResearchSex differences in stress-induced alcohol intake: a review of preclinical studies focused on amygdala and inflammatory pathways
Mineur YS, Garcia-Rivas V, Thomas MA, Soares AR, McKee SA, Picciotto MR. Sex differences in stress-induced alcohol intake: a review of preclinical studies focused on amygdala and inflammatory pathways. Psychopharmacology 2022, 239: 2041-2061. PMID: 35359158, PMCID: PMC9704113, DOI: 10.1007/s00213-022-06120-w.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAlcohol intakeInflammatory pathwaysAlcohol drinkingStress-induced alcohol drinkingSex differencesSex-dependent effectsStress-induced alcoholEffects of stressPreclinical behavioral modelsAlcohol-dependent behaviorsMicroglial activationClinical studiesPreclinical studiesInflammatory signalingNeuronal functionAlcohol seekingIntakeFuture studiesDrinkingDifferencesAmygdalaPathwayStudyWomen
2021
Phase II double blinded randomized placebo-controlled trial of minocycline to ameliorate chemotherapy-induced cognitive changes in breast cancer (BC) patients.
Sharpe J, Schnell P, Knopp M, Binzel K, Magyer M, Cherian M, Gatti-Mays M, Pariser A, Wesolowski R, Sardesai S, VanDeusen J, Stover D, Ramaswamy B, Williams N, DeVries A, Shinde N, Orchard T, Lustberg M. Phase II double blinded randomized placebo-controlled trial of minocycline to ameliorate chemotherapy-induced cognitive changes in breast cancer (BC) patients. Journal Of Clinical Oncology 2021, 39: e12528-e12528. DOI: 10.1200/jco.2021.39.15_suppl.e12528.Peer-Reviewed Original ResearchPET/CT imagingPET/CTCytokine levelsMicroglial activationCT imagingF-fluorodeoxyglucoseDouble-blinded randomized placebo-controlled trialBlinded randomized placebo-controlled trialChemotherapy-induced cognitive changesRandomized placebo-controlled trialCognitive functionPlacebo-controlled trialInflammatory cytokine levelsBreast cancer patientsCognitive changesCT brain imagingAC therapyDaily minocyclinePotent mitigatorNeoadjuvant chemotherapyPlacebo groupInflammatory markersInflammatory changesMedian ageMinocycline groupSoluble 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
Gene expression in the epileptic (EL) mouse hippocampus
Lee TS, Li AY, Rapuano A, Mantis J, Eid T, Seyfried TN, de Lanerolle NC. Gene expression in the epileptic (EL) mouse hippocampus. Neurobiology Of Disease 2020, 147: 105152. PMID: 33153970, DOI: 10.1016/j.nbd.2020.105152.Peer-Reviewed Original ResearchConceptsTemporal lobe epilepsyHuman temporal lobe epilepsySeizure focusHippocampal seizure focusRole of neurogliaExtensive neuronal lossMolecular changesEpileptic miceMicroglial activationNeuronal lossNeuron lossEl miceLobe epilepsySeizure modelHippocampal fieldsSeizure generationPathological changesPaucity of studiesMouse hippocampusAnimal modelsHeat shock proteinsNormal populationPathological processesExpression levelsEpilepsyPTSD is associated with neuroimmune suppression: evidence from PET imaging and postmortem transcriptomic studies
Bhatt S, Hillmer AT, Girgenti MJ, Rusowicz A, Kapinos M, Nabulsi N, Huang Y, Matuskey D, Angarita GA, Esterlis I, Davis MT, Southwick SM, Friedman MJ, Duman R, Carson R, Krystal J, Pietrzak R, Cosgrove K. PTSD is associated with neuroimmune suppression: evidence from PET imaging and postmortem transcriptomic studies. Nature Communications 2020, 11: 2360. PMID: 32398677, PMCID: PMC7217830, DOI: 10.1038/s41467-020-15930-5.Peer-Reviewed Original ResearchMeSH KeywordsAcetamidesAdaptor Proteins, Signal TransducingAdultBrainCase-Control StudiesFemaleGene Expression ProfilingHealthy VolunteersHumansMaleMicrogliaMiddle AgedPositron-Emission TomographyPyridinesRadiopharmaceuticalsReceptors, GABAReceptors, Tumor Necrosis Factor, Member 14Sex FactorsStress Disorders, Post-TraumaticYoung AdultConceptsPosttraumatic stress disorderPeripheral immune activationImmune activationHigher C-reactive protein levelsC-reactive protein levelsTSPO availabilityTranslocator proteinBrain microglial activationTomography brain imagingStress-related pathophysiologyPositron emission tomography (PET) brain imagingNeuroimmune activationMicroglial activationPTSD symptom severityImmunologic regulationPostmortem studiesPTSD subgroupHealthy individualsSymptom severityTrauma exposurePTSD groupStress disorderLower relative expressionBrain imagingPET imagingHippocampal microglial activation triggers a neurotoxic-specific astrocyte response and mediates etomidate-induced long-term synaptic inhibition
Li D, Chen M, Meng T, Fei J. Hippocampal microglial activation triggers a neurotoxic-specific astrocyte response and mediates etomidate-induced long-term synaptic inhibition. Journal Of Neuroinflammation 2020, 17: 109. PMID: 32264970, PMCID: PMC7140340, DOI: 10.1186/s12974-020-01799-0.Peer-Reviewed Original ResearchConceptsPostoperative cognitive dysfunctionAstrocyte activationPathological stageAstrocyte responseMicroglial activationCognitive functionSynaptic inhibitionCognitive dysfunctionNovel object recognition testHippocampal microglial activationInitial pathological stageInhibitory postsynaptic currentsSignificant microglial activationLate pathological stageEarly pathological stageMonth old miceObject recognition testMorris water mazeQuantitative polymerase chain reactionMagnetic-activated cell sortingActivated microgliaSedative dosePostsynaptic currentsPolymerase chain reactionMicroglia
2019
FTY720 Inhibits MPP+-Induced Microglial Activation by Affecting NLRP3 Inflammasome Activation
Yao S, Li L, Sun X, Hua J, Zhang K, Hao L, Liu L, Shi D, Zhou H. FTY720 Inhibits MPP+-Induced Microglial Activation by Affecting NLRP3 Inflammasome Activation. Journal Of Neuroimmune Pharmacology 2019, 14: 478-492. PMID: 31069623, DOI: 10.1007/s11481-019-09843-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntiparkinson AgentsApoptosisCell LineCorpus StriatumCytokinesDopaminergic NeuronsDrug Evaluation, PreclinicalExploratory BehaviorFingolimod HydrochlorideInflammasomesMaleMiceMice, Inbred C57BLMicrogliaMitochondriaMPTP PoisoningNeuroprotective AgentsNLR Family, Pyrin Domain-Containing 3 ProteinParkinsonian DisordersPars CompactaReactive Oxygen SpeciesRotarod Performance TestSignal TransductionConceptsTherapeutic effects of FTY720Effect of FTY720Therapeutic effectNLRP3 inflammasome activationDopaminergic neuronsMicroglial activationP65 activationInflammasome activationSubcutaneous injection of MPTPMPTP-induced microglial activationIncreased dopamine releaseMPTP-induced behavioral deficitsDamage to dopaminergic neuronsTumor necrosis factor-aAnimal models of PDInjection of MPTPROS generationSubstantia nigra pars compactaDecreased NLRP3 inflammasome activationParkinson's diseaseInterleukin (IL)-6Production of interleukin (IL)-6Degeneration of dopaminergic neuronsLoss of dopaminergic neuronsActivation of microgliaTargeting neuroinflammation with minocycline in heavy drinkers
Petrakis IL, Ralevski E, Gueorguieva R, Sloan ME, Devine L, Yoon G, Arias AJ, Sofuoglu M. Targeting neuroinflammation with minocycline in heavy drinkers. Psychopharmacology 2019, 236: 3013-3021. PMID: 30919006, PMCID: PMC6764907, DOI: 10.1007/s00213-019-05205-3.Peer-Reviewed Original ResearchConceptsPro-inflammatory cytokine releaseEthanol-induced inflammationMicroglial activationCytokine levelsCytokine releaseHeavy drinkersSecond-generation tetracycline antibioticDose of minocyclinePlacebo-controlled trialSerum cytokine levelsSubjective responsesBaseline cytokine levelsEffects of minocyclineViable treatment strategyShort-term treatmentAlcohol use disorderNeuroimmune modulationMinocycline treatmentNeuroimmune signalingMinocycline effectsIntravenous ethanolEthanol intakeSedative responseTreatment strategiesPreclinical studiesmTOR Hyperactivity Levels Influence the Severity of Epilepsy and Associated Neuropathology in an Experimental Model of Tuberous Sclerosis Complex and Focal Cortical Dysplasia
Nguyen LH, Mahadeo T, Bordey A. mTOR Hyperactivity Levels Influence the Severity of Epilepsy and Associated Neuropathology in an Experimental Model of Tuberous Sclerosis Complex and Focal Cortical Dysplasia. Journal Of Neuroscience 2019, 39: 2762-2773. PMID: 30700531, PMCID: PMC6445990, DOI: 10.1523/jneurosci.2260-18.2019.Peer-Reviewed Original ResearchConceptsFocal cortical dysplasiaTuberous sclerosis complexSeverity of epilepsyRapamycin (mTOR) pathway genesPersonalized medicine strategiesAssociated neuropathologyCortical dysplasiaMouse modelActivity levelsPathogenic variantsEpileptogenic cortical malformationsNeuronal soma sizeMedicine strategiesPatient variantsMechanistic targetSevere epilepsy phenotypePreclinical drug testingHyperactivity levelsDose-dependent mannerMicroglial activationSeizure frequencyRecurrent seizuresCortical malformationsIntractable epilepsyClinical assessment
2018
CSF concentrations of soluble TREM2 as a marker of microglial activation in HIV-1 infection
Gisslén M, Heslegrave A, Veleva E, Yilmaz A, Andersson LM, Hagberg L, Spudich S, Fuchs D, Price RW, Zetterberg H. CSF concentrations of soluble TREM2 as a marker of microglial activation in HIV-1 infection. Neurology Neuroimmunology & Neuroinflammation 2018, 6: e512. PMID: 30568991, PMCID: PMC6278890, DOI: 10.1212/nxi.0000000000000512.Peer-Reviewed Original ResearchConceptsHIV-1 infectionHIV-negative controlsMicroglial activationNeuronal injuryCSF concentrationsUntreated HIV-1-infected patientsHIV-1 disease severityHIV-1-infected adultsMacrophage/microglial activationHIV-1-infected patientsRetrospective cross-sectional studyUntreated HIV-1 infectionCNS immune activationCSF sTREM2 levelsSuppressive antiretroviral treatmentT-cell countsMicroglial activation markersT cell lossLevels of CSFNeurofilament light proteinCross-sectional studyCSF sTREM2STREM2 levelsAntiretroviral treatmentActivation markersNatalizumab Treatment of Multiple Sclerosis Leads to Diminished Microglial Activation in the Normal Appearing White Matter (P3.390)
Airas L, Sucksdorff M, Tuisku J, Rissanen E. Natalizumab Treatment of Multiple Sclerosis Leads to Diminished Microglial Activation in the Normal Appearing White Matter (P3.390). Neurology 2018, 90 DOI: 10.1212/wnl.90.15_supplement.p3.390.Peer-Reviewed Original Research
2017
High Number of Activated CD8+ T Cells Targeting HIV Antigens Are Present in Cerebrospinal Fluid in Acute HIV Infection
Kessing CF, Spudich S, Valcour V, Cartwright P, Chalermchai T, Fletcher JL, Takata H, Nichols C, Josey B, Slike B, Krebs S, Sailsuta N, Lerdlum S, Jagodzinski L, Tipsuk S, Suttichom D, Rattanamanee S, Zetterberg H, Hellmuth J, Phanuphak N, Robb M, Michael N, Ananworanich J, Trautmann L. High Number of Activated CD8+ T Cells Targeting HIV Antigens Are Present in Cerebrospinal Fluid in Acute HIV Infection. JAIDS Journal Of Acquired Immune Deficiency Syndromes 2017, 75: 108-117. PMID: 28177966, PMCID: PMC5388590, DOI: 10.1097/qai.0000000000001301.Peer-Reviewed Original ResearchConceptsAcute HIV infectionCD8 T cellsChronic HIV infectionHIV infectionT cellsCerebrospinal fluidCD8 T cell effector functionsHIV-specific CD8 T cellsCentral nervous system infiltrationT cell effector functionT cell receptor repertoireCSF HIV RNACombination antiretroviral therapyTCR Vbeta repertoireCell effector functionsCell receptor repertoireHIV specificitiesAntiretroviral therapyCNS inflammationHIV RNAVbeta repertoireMicroglial activationActivated CD8HIV antigenHIV epitopesIn vivo imaging of translocator protein, a marker of activated microglia, in alcohol dependence
Hillmer AT, Sandiego CM, Hannestad J, Angarita GA, Kumar A, McGovern EM, Huang Y, O'Connor KC, Carson RE, O'Malley SS, Cosgrove KP. In vivo imaging of translocator protein, a marker of activated microglia, in alcohol dependence. Molecular Psychiatry 2017, 22: 1759-1766. PMID: 28242869, PMCID: PMC5573660, DOI: 10.1038/mp.2017.10.Peer-Reviewed Original ResearchMeSH KeywordsAcetamidesAdultAlcoholismBrainBrain MappingCarbon RadioisotopesCells, CulturedCytokinesFemaleHumansInflammationLipopolysaccharidesMaleMicrogliaMonocytesNeuroimagingPolymorphism, Single NucleotidePositron-Emission TomographyPyridinesRadiopharmaceuticalsReceptors, GABASeverity of Illness IndexConceptsAlcohol-dependent subjectsAlcohol dependenceTSPO levelsTranslocator proteinProinflammatory cytokine interleukin-6Peripheral immune profilePeripheral immune responseCytokine interleukin-6Absence of lipopolysaccharideSubset of subjectsAlcohol use disorderPositron emission tomographyAlcohol-dependent individualsMicroglial activationImmune profileNeuroimmune systemCytokine expressionBrain levelsProinflammatory responseInterleukin-6Healthy controlsInterleukin-8Immune responseLast drinkUse disordersImmediate initiation of cART is associated with lower levels of cerebrospinal fluid YKL-40, a marker of microglial activation, in HIV-1 infection
Peluso MJ, Valcour V, Phanuphak N, Ananworanich J, Fletcher JL, Chalermchai T, Krebs SJ, Robb ML, Hellmuth J, Gisslén M, Zetterberg H, Spudich S. Immediate initiation of cART is associated with lower levels of cerebrospinal fluid YKL-40, a marker of microglial activation, in HIV-1 infection. AIDS 2017, 31: 247-252. PMID: 27819802, PMCID: PMC5844231, DOI: 10.1097/qad.0000000000001314.Peer-Reviewed Original ResearchConceptsChronic HIV-1 infectionCombination antiretroviral therapyCerebrospinal fluid (CSF) YKL-40Group of HIVHIV-1 infectionYKL-40Treatment initiationUntreated chronic HIV-1 infectionMedian YKL-40Early HIV infectionCSF YKL-40Chemokine ligand 10Neurofilament light chainCross-sectional studyMann-Whitney testAntiretroviral therapyHIV neuropathogenesisMicroglial activationHIV infectionPrognostic valueChi groupMicroglial cellsAHI groupImmediate initiationBlood sampling
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