title: Degeneration in different parkinsonian syndromes relates to astrocyte type and astrocyte protein expression.
abstract: The reactive changes in different types of astrocytes were analyzed in parkinsonian syndromes in order to identify common reactions and their relationship to disease severity. Immunohistochemistry was used on formalin-fixed, paraffin-embedded sections from the putamen, pons, and substantia nigra from 13 Parkinson disease (PD), 29 multiple-system atrophy (MSA), 34 progressive supranuclear palsy (PSP), 10 corticobasal degeneration(CBD), and 13 control cases. Classic reactive astrocytes were observed in MSA, PSP, and CBD, but not PD cases; the extent of reactivity correlated with indices of neurodegeneration and disease stage. Approximately 40% to 45% of subcortical astrocytes in PD and PSP accumulated alpha-synuclein and phospho-tau, respectively; subcortical astrocytes in MSA and CBD cases did not accumulate these proteins. Protoplasmic astrocytes were identified from fibrous astrocytes by their expression of parkin coregulated gene and apolipoprotein D, and accumulated abnormal proteins in PD, PSP, and CBD, but not MSA. The increased reactivity of parkin coregulated gene-immunoreactive protoplasmic astrocytes correlated with parkin expression in PSP and CBD. Nonreactive protoplasmic astrocytes were observed in PD and MSA cases; in PD, they accumulated alpha-synuclein, suggesting that the attenuated response might be due to an increase in the level of alpha-synuclein. These heterogeneous astroglial responses in PD, MSA, PSP, and CBD indicate distinct underlying pathogenic mechanisms in each disorder.
authors.affiliation: Prince of Wales Medical Research Institute and the University of New South Wales, Barker Street, Randwick, Sydney, Australia.
authors.forename: Yun Ju C
authors.initials: YJ
authors.lastname: Song
authors.forename: Glenda M
authors.initials: GM
authors.lastname: Halliday
authors.forename: Janice L
authors.initials: JL
authors.lastname: Holton
authors.forename: Tammaryn
authors.initials: T
authors.lastname: Lashley
authors.forename: Seán S
authors.initials: SS
authors.lastname: O'Sullivan
authors.forename: Heather
authors.initials: H
authors.lastname: McCann
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lees
authors.forename: Tetsutaro
authors.initials: T
authors.lastname: Ozawa
authors.forename: David R
authors.initials: DR
authors.lastname: Williams
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Lockhart
authors.forename: Tamas R
authors.initials: TR
authors.lastname: Revesz
mesh_terms: D053399:Apolipoproteins D / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D026901:Membrane Transport Proteins / Q000378:metabolism; D019578:Multiple System Atrophy / Q000378:metabolism / Q000473:pathology; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology; D020734:Parkinsonian Disorders / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D011149:Pons / Q000378:metabolism* / Q000473:pathology; D011699:Putamen / Q000378:metabolism* / Q000473:pathology; D012720:Severity of Illness Index; D013378:Substantia Nigra / Q000378:metabolism* / Q000473:pathology; D013494:Supranuclear Palsy, Progressive / Q000378:metabolism / Q000473:pathology; D051844:alpha-Synuclein / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: C024328:APOD protein, human; D053399:Apolipoproteins D; D006023:Glycoproteins; C054369:MAPT protein, human; D026901:Membrane Transport Proteins; D051844:alpha-Synuclein; D016875:tau Proteins