Degeneration in Different Parkinsonian Syndromes Relates to Astrocyte Type and Astrocyte Protein Expression

• Published in: Journal of neuropathology and experimental neurology 2009-10, Vol.68 (10), p.1073-1083
• Main Authors: Song, Yun Ju C, Halliday, Glenda M, Holton, Janice L, Lashley, Tammaryn, O'Sullivan, Seán S, McCann, Heather, Lees, Andrew J, Ozawa, Tetsutaro, Williams, David R, Lockhart, Paul J, Revesz, Tamas R
• Format: Article
• Language: English
• Subjects: alpha-Synuclein - metabolism; Apolipoproteins D - metabolism; Astrocytes - metabolism; Astrocytes - pathology; Biological and medical sciences; Glycoproteins - metabolism; Humans; Immunohistochemistry; Malformations of the nervous system; Medical sciences; Membrane Transport Proteins - metabolism; Multiple System Atrophy - metabolism; Multiple System Atrophy - pathology; Nerve Degeneration - metabolism; Nerve Degeneration - pathology; Neurology; Parkinson Disease - metabolism; Parkinson Disease - pathology; Parkinsonian Disorders - metabolism; Parkinsonian Disorders - pathology; Phosphorylation; Pons - metabolism; Pons - pathology; Putamen - metabolism; Putamen - pathology; Severity of Illness Index; Substantia Nigra - metabolism; Substantia Nigra - pathology; Supranuclear Palsy, Progressive - metabolism; Supranuclear Palsy, Progressive - pathology; tau Proteins - metabolism
• ISSN: 0022-3069; 1554-6578
• DOI: 10.1097/NEN.0b013e3181b66f1b

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 α-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 α-synuclein, suggesting that the attenuated response might be due to an increase in the level of α-synuclein. These heterogenous astroglial responses in PD, MSA, PSP, and CBD indicate distinct underlying pathogenic mechanisms in each disorder.