Alpha-synuclein immunoreactivity and ultrastructural study of glial cytoplasmic inclusions in multiple system atrophy.

Abstract

OBJECTIVE:

To understand the possible pathogenesis of sporadic multiple system atrophy (MSA).

METHODS:

The immunoreactivity and ultrastructural features of glial cytoplasmic inclusions (GCIs) in 12 autopsy patients with MSA and 4 normal control groups were studied. All regional sections from each subject were evaluated with HE staining, Klüver-Barrera (KB), Holzer's, modified Gallyas-Braak's (GB) methods and immunohistochemical staining with alpha-synuclein and ubiquitin antibodies. Pontine white matter with abundant GCIs from case 1 was examined, using conventional electron microscopy, Gallyas-Braak's electron microscopy and immunoelectron microscopy.

RESULTS:

The presence of GCIs as constantly demonstrated in all MSA patients. Strong alpha-synuclein immunoreactivity was observed in all of the ubiquitinated GCIs. However, the density of alpha-synuclein positive GCIs differed from case to case, and there was no relationship between the density of GCIs and age, sex, or MSA subtype. Ultrastructural features indicated that argyrophilic granule-associated filaments of about 25 nm in diameter were the predominant constituents of GCIs, and the anti alpha-synuclein antibody selectively labeled in these filaments. No GCIs and alpha-synuclein immunoreaction were found in control brain tissues.

CONCLUSIONS:

GCI was a pathognomonic change in sporadic MSA patients. Accumulation of alpha-synuclein in GCIs may occur during the early stags of MSA. Seletcive alpha-synuclein positive abnormal microtubules in GCIs therefore play an important role in the pathogenesis of MSA.

• Authors: Yin Wang, Chuanzhen Lü, Zhurong Ye
• Journal: Chinese medical journal (Chin Med J (Engl)) Vol. 115 Issue 10 Pg. 1491-5 (Oct 2002) ISSN: 0366-6999 [Print] China
• PMID: 12490094 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Nerve Tissue Proteins
• SNCA protein, human
• Synucleins
• alpha-Synuclein

Topics

• Aged
• Aged, 80 and over
• Female
• Humans
• Immunohistochemistry
• Inclusion Bodies (ultrastructure)
• Male
• Microscopy, Immunoelectron
• Middle Aged
• Multiple System Atrophy (etiology, metabolism, pathology)
• Nerve Tissue Proteins (analysis)
• Neuroglia (ultrastructure)
• Synucleins
• alpha-Synuclein