2019
The landscape of myeloid and astrocyte phenotypes in acute multiple sclerosis lesions
Park C, Ponath G, Levine-Ritterman M, Bull E, Swanson EC, De Jager PL, Segal BM, Pitt D. The landscape of myeloid and astrocyte phenotypes in acute multiple sclerosis lesions. Acta Neuropathologica Communications 2019, 7: 130. PMID: 31405387, PMCID: PMC6689891, DOI: 10.1186/s40478-019-0779-2.Peer-Reviewed Original ResearchConceptsMultiple sclerosis lesionsLesion rimAstrocyte phenotypeMyeloid cellsSclerosis lesionsActive multiple sclerosis lesionsAcute multiple sclerosis lesionsGlial activation markersActive MS lesionsNovel therapeutic targetDifferent lesion stagesPredominant cell typeAcute demyelinationDemyelinating lesionsCell typesActivation markersChronic inflammationDistinct myeloidCell-extrinsic factorsGlial cellsPhenotypic subsetsLesion stageGlial phenotypeMS lesionsLesion cells
2018
Enhanced astrocyte responses are driven by a genetic risk allele associated with multiple sclerosis
Ponath G, Lincoln MR, Levine-Ritterman M, Park C, Dahlawi S, Mubarak M, Sumida T, Airas L, Zhang S, Isitan C, Nguyen TD, Raine CS, Hafler DA, Pitt D. Enhanced astrocyte responses are driven by a genetic risk allele associated with multiple sclerosis. Nature Communications 2018, 9: 5337. PMID: 30559390, PMCID: PMC6297228, DOI: 10.1038/s41467-018-07785-8.Peer-Reviewed Original ResearchConceptsMultiple sclerosisAstrocyte responseRisk variantsLocal autoimmune inflammationPeripheral immune cellsCentral nervous system cellsPeripheral immune systemCultured human astrocytesNervous system cellsNF-κB signalingCNS accessDysfunctional lymphocytesAstroglial functionAutoimmune inflammationLymphocytic infiltrateLymphocyte recruitmentImmune cellsGenetic risk allelesGenetic risk variantsMS lesionsMS susceptibilityHuman astrocytesLesion sizeImmune systemSystem cellsAstrocytes play a crucial role in the formation and evolution of MS lesions – Yes
Pitt D, Ponath G. Astrocytes play a crucial role in the formation and evolution of MS lesions – Yes. Multiple Sclerosis Journal 2018, 25: 15-17. PMID: 30136895, DOI: 10.1177/1352458518793026.Peer-Reviewed Original ResearchThe Role of Astrocytes in Multiple Sclerosis
Ponath G, Park C, Pitt D. The Role of Astrocytes in Multiple Sclerosis. Frontiers In Immunology 2018, 9: 217. PMID: 29515568, PMCID: PMC5826071, DOI: 10.3389/fimmu.2018.00217.Peer-Reviewed Original ResearchConceptsRole of astrocytesImmune cell accessCentral nervous systemMultiple sclerosis lesionsAstrocyte activationMultiple sclerosisGlial scarAstrocyte functionMS treatmentMS lesionsNervous systemAstrocytesSclerosis lesionsLesion formationFunctional polarizationLesionsCell accessSclerosisInflammationPathogenesis
2016
Myelin phagocytosis by astrocytes after myelin damage promotes lesion pathology
Ponath G, Ramanan S, Mubarak M, Housley W, Lee S, Sahinkaya FR, Vortmeyer A, Raine CS, Pitt D. Myelin phagocytosis by astrocytes after myelin damage promotes lesion pathology. Brain 2016, 140: 399-413. PMID: 28007993, PMCID: PMC5841057, DOI: 10.1093/brain/aww298.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnimalsAnimals, NewbornAstrocytesCell ProliferationCells, CulturedChild, PreschoolCultureCytokinesDemyelinating Autoimmune Diseases, CNSEndocytosisFemaleHumansHydrazonesMacrophagesMaleMiddle AgedMyelin SheathPhagocytosisRatsRats, Sprague-DawleyStrokeTime FactorsTransforming Growth Factor betaConceptsMyelin injuryMyelin phagocytosisMyelin debrisMultiple sclerosis lesionsMultiple sclerosisLesion pathologySclerosis lesionsAcute multiple sclerosis lesionsCentral nervous system pathologyProgressive multifocal leukoencephalopathyNervous system pathologySecretion of chemokinesNF-κB activationElevated chemokine expressionHypertrophic astrocytesMost astrocytesMyelin uptakeMultifocal leukoencephalopathyFirst-line responseAcute lesionsMyelin damageReactive astrocytesChemokine expressionAstroglial responseImmune cells
2003
Glutamate uptake by oligodendrocytes
Pitt D, Nagelmeier IE, Wilson HC, Raine CS. Glutamate uptake by oligodendrocytes. Neurology 2003, 61: 1113-1120. PMID: 14581674, DOI: 10.1212/01.wnl.0000090564.88719.37.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAstrocytesAutoradiographyBiological TransportCell SurvivalCells, CulturedDose-Response Relationship, DrugExcitatory Amino Acid Transporter 1Excitatory Amino Acid Transporter 2FemaleGene ExpressionGlutamic AcidHumansIn Situ HybridizationMaleMiddle AgedMultiple SclerosisNeurotoxinsOligodendrogliaRNA, MessengerSpinal CordTritiumTumor Necrosis Factor-alphaConceptsMS white matterEAAT-2EAAT-1White matterExtracellular glutamateGlutamate uptakePredominant cellsHuman oligodendrocytesGlutamate removalProinflammatory cytokine tumor necrosisHuman white matterNormal human white matterCommon pathologic eventGlutamate transporter expressionGlutamate receptor expressionCytokine tumor necrosisExcess extracellular glutamateInhibited glutamate uptakeHigh extracellular glutamateSubsequent overstimulationExcitotoxic damageGlutamate excitotoxicityGlutamate clearanceTumor necrosisReceptor expression