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Progressive accumulation of ubiquitin and disappearance of alpha-synuclein epitope in multiple system atrophy-associated glial cytoplasmic inclusions: triple fluorescence study combined with Gallyas-Braak method.
Acta Neuropathol. 2005 Oct; 110(4):417-25.AN

Abstract

Alpha-synuclein (alphaS) and ubiquitin (Ub) are shared constituents of glial cytoplasmic inclusions (GCIs) and Lewy bodies (LBs), both composed of fibrillary structures. Staining profiles of GCIs were investigated with triple immunofluorescence involving immunostaining for alphaS and Ub, both amplified with catalyzed reporter deposition, and a fluorochrome, thiazin red (TR) that has an affinity to fibrillary structures. After observation for the triple-fluorescent images, the sections were subsequently stained with the Gallyas-Braak method. Sections of putamen, cerebellar white matter and motor cortex from patients suffering from multiple system atrophy (MSA) with varying duration of the disease (4-15 years) were quantified for these staining profiles of Gallyas-positive GCIs. Although most of GCIs were positive for Ub and variably positive for alphaS, they were consistently negative for TR. The result was opposite in LBs in Lewy body disease with variable affinity to TR, suggesting that the construction of GCIs is different from that of LBs. These four staining features (alphaS, Ub, TR and Gallyas) alone failed to exhibit apparent correlation with disease duration, lesion site or severity of degeneration as reported previously. The fraction of alphaS-negative and Ub-positive GCIs, however, linearly increased along the disease progression, while that of alphaS-positive and Ub-negative GCIs decreased in contrast. This reciprocal change suggests that alphaS immunoreactivity in GCIs is being replaced by Ub immunoreactivity during the disease progression, which resulted in the ultimate predominance of alphaS-negative and Ub-positive GCIs in the most advanced case. Interestingly, this predominance of alphaS-negative and Ub-positive GCIs was a feature of motor cortex, where degeneration usually remains mild in spite of robust appearance of Gallyas-positive GCIs. Another fraction, alphaS-positive and Ub-positive GCIs were frequent in cerebellar white matter, suggesting that GCI evolution is heterogeneous and dependent also on area examined. Progressive accumulation of Ub with concomitant disappearance of alphaS epitope and their colocalization, partly shared with LBs, may represent a process of GCI formation, possibly linked to an aspect of degeneration in MSA.

Authors+Show Affiliations

Department of Neurology, Tokyo Metropolitan Neurological Hospital, Tokyo, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16133540

Citation

Sakamoto, Masaki, et al. "Progressive Accumulation of Ubiquitin and Disappearance of Alpha-synuclein Epitope in Multiple System Atrophy-associated Glial Cytoplasmic Inclusions: Triple Fluorescence Study Combined With Gallyas-Braak Method." Acta Neuropathologica, vol. 110, no. 4, 2005, pp. 417-25.
Sakamoto M, Uchihara T, Nakamura A, et al. Progressive accumulation of ubiquitin and disappearance of alpha-synuclein epitope in multiple system atrophy-associated glial cytoplasmic inclusions: triple fluorescence study combined with Gallyas-Braak method. Acta Neuropathol. 2005;110(4):417-25.
Sakamoto, M., Uchihara, T., Nakamura, A., Mizutani, T., & Mizusawa, H. (2005). Progressive accumulation of ubiquitin and disappearance of alpha-synuclein epitope in multiple system atrophy-associated glial cytoplasmic inclusions: triple fluorescence study combined with Gallyas-Braak method. Acta Neuropathologica, 110(4), 417-25.
Sakamoto M, et al. Progressive Accumulation of Ubiquitin and Disappearance of Alpha-synuclein Epitope in Multiple System Atrophy-associated Glial Cytoplasmic Inclusions: Triple Fluorescence Study Combined With Gallyas-Braak Method. Acta Neuropathol. 2005;110(4):417-25. PubMed PMID: 16133540.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Progressive accumulation of ubiquitin and disappearance of alpha-synuclein epitope in multiple system atrophy-associated glial cytoplasmic inclusions: triple fluorescence study combined with Gallyas-Braak method. AU - Sakamoto,Masaki, AU - Uchihara,Toshiki, AU - Nakamura,Ayako, AU - Mizutani,Toshio, AU - Mizusawa,Hidehiro, Y1 - 2005/08/25/ PY - 2004/12/07/received PY - 2005/07/04/accepted PY - 2005/02/02/revised PY - 2005/9/1/pubmed PY - 2007/10/20/medline PY - 2005/9/1/entrez SP - 417 EP - 25 JF - Acta neuropathologica JO - Acta Neuropathol VL - 110 IS - 4 N2 - Alpha-synuclein (alphaS) and ubiquitin (Ub) are shared constituents of glial cytoplasmic inclusions (GCIs) and Lewy bodies (LBs), both composed of fibrillary structures. Staining profiles of GCIs were investigated with triple immunofluorescence involving immunostaining for alphaS and Ub, both amplified with catalyzed reporter deposition, and a fluorochrome, thiazin red (TR) that has an affinity to fibrillary structures. After observation for the triple-fluorescent images, the sections were subsequently stained with the Gallyas-Braak method. Sections of putamen, cerebellar white matter and motor cortex from patients suffering from multiple system atrophy (MSA) with varying duration of the disease (4-15 years) were quantified for these staining profiles of Gallyas-positive GCIs. Although most of GCIs were positive for Ub and variably positive for alphaS, they were consistently negative for TR. The result was opposite in LBs in Lewy body disease with variable affinity to TR, suggesting that the construction of GCIs is different from that of LBs. These four staining features (alphaS, Ub, TR and Gallyas) alone failed to exhibit apparent correlation with disease duration, lesion site or severity of degeneration as reported previously. The fraction of alphaS-negative and Ub-positive GCIs, however, linearly increased along the disease progression, while that of alphaS-positive and Ub-negative GCIs decreased in contrast. This reciprocal change suggests that alphaS immunoreactivity in GCIs is being replaced by Ub immunoreactivity during the disease progression, which resulted in the ultimate predominance of alphaS-negative and Ub-positive GCIs in the most advanced case. Interestingly, this predominance of alphaS-negative and Ub-positive GCIs was a feature of motor cortex, where degeneration usually remains mild in spite of robust appearance of Gallyas-positive GCIs. Another fraction, alphaS-positive and Ub-positive GCIs were frequent in cerebellar white matter, suggesting that GCI evolution is heterogeneous and dependent also on area examined. Progressive accumulation of Ub with concomitant disappearance of alphaS epitope and their colocalization, partly shared with LBs, may represent a process of GCI formation, possibly linked to an aspect of degeneration in MSA. SN - 0001-6322 UR - https://www.unboundmedicine.com/medline/citation/16133540/Progressive_accumulation_of_ubiquitin_and_disappearance_of_alpha_synuclein_epitope_in_multiple_system_atrophy_associated_glial_cytoplasmic_inclusions:_triple_fluorescence_study_combined_with_Gallyas_Braak_method_ L2 - https://dx.doi.org/10.1007/s00401-005-1066-9 DB - PRIME DP - Unbound Medicine ER -