2024
Microglia-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 symptomsAnhedonia
2020
Acute neuroimmune stimulation impairs verbal memory in adults: A PET brain imaging study
Woodcock EA, Hillmer AT, Sandiego CM, Maruff P, Carson RE, Cosgrove KP, Pietrzak RH. Acute neuroimmune stimulation impairs verbal memory in adults: A PET brain imaging study. Brain Behavior And Immunity 2020, 91: 784-787. PMID: 33002632, PMCID: PMC7749814, DOI: 10.1016/j.bbi.2020.09.027.Peer-Reviewed Original ResearchConceptsMemory processesCognitive dysfunctionHippocampal memory processesBrain imaging studiesExecutive processesVerbal learningVerbal memoryExperimental paradigmCognitive deficitsPositron emission tomographyGreater decrementNeuroinflammatory dysfunctionNeurologic disordersPrevious findingsHealthy adultsDevelopment studiesMarker of microgliaImaging studiesNeuroimmune responseLPS administrationNeuroinflammatory signalingAdultsPreclinical findingsExperimental inductionDisordersPTSD 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 imaging
2017
In 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 disorders
2015
Imaging robust microglial activation after lipopolysaccharide administration in humans with PET
Sandiego CM, Gallezot JD, Pittman B, Nabulsi N, Lim K, Lin SF, Matuskey D, Lee JY, O’Connor K, Huang Y, Carson RE, Hannestad J, Cosgrove KP. Imaging robust microglial activation after lipopolysaccharide administration in humans with PET. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 12468-12473. PMID: 26385967, PMCID: PMC4603509, DOI: 10.1073/pnas.1511003112.Peer-Reviewed Original ResearchConceptsMicroglial activationBrain microglial activationLPS administrationInflammatory cytokinesLPS challengeRobust microglial activationSystemic LPS challengeActivation of microgliaInnate immune cellsVital sign changesHealthy male subjectsEscherichia coli lipopolysaccharidePositron emission tomography (PET) radiotracerNeuroinflammatory responseSystemic inflammationLipopolysaccharide administrationAntiinflammatory effectsBlood levelsImmune cellsNew medicationsSystemic administrationColi lipopolysaccharidePET scansPsychiatric diseasesMale subjects
2012
Endotoxin-induced systemic inflammation activates microglia: [11C]PBR28 positron emission tomography in nonhuman primates
Hannestad J, Gallezot JD, Schafbauer T, Lim K, Kloczynski T, Morris ED, Carson RE, Ding YS, Cosgrove KP. Endotoxin-induced systemic inflammation activates microglia: [11C]PBR28 positron emission tomography in nonhuman primates. NeuroImage 2012, 63: 232-239. PMID: 22776451, PMCID: PMC3699786, DOI: 10.1016/j.neuroimage.2012.06.055.Peer-Reviewed Original ResearchConceptsPositron emission tomographySystemic inflammationMultiple sclerosisInterleukin-6Interleukin-8Translocator proteinEndotoxin-induced systemic inflammationLevels of TSPOEmission tomographyTumor necrosis factor alphaSystemic inflammatory processActivation of microgliaSerum IL-1βIL-6 levelsCourse of diseaseEffects of LPSImportant clinical questionsNecrosis factor alphaInterleukin-1 betaNonhuman primate brainE. coli lipopolysaccharideRegional time-activity dataLocal tissue damageTwo-tissue compartmental modelTotal ligand binding