Immunohistochemical localization of aggresomal proteins in glial cytoplasmic inclusions in multiple system atrophy.
OBJECTIVE
Multiple system atrophy (MSA) is pathologically characterized by the formation of α-synuclein-containing glial cytoplasmic inclusions (GCIs) in oligodendrocytes. However, the mechanisms of GCI formation are not fully understood. Cellular machinery for the formation of aggresomes has been linked to the biogenesis of the Lewy body, a characteristic α-synuclein-containing inclusion of Parkinson's disease and dementia with Lewy bodies. Here, we examined whether GCIs contain the components of aggresomes by immunohistochemistry.


METHODS
Sections from five patients with MSA were stained immunohistochemically with antibodies against aggresome-related proteins and analysed in comparison with sections from five patients with no neurological disease. We evaluated the presence or absence of aggresome-related proteins in GCIs by double immunofluorescence and immunoelectron microscopy.


RESULTS
GCIs were clearly immunolabelled with antibodies against aggresome-related proteins, such as γ-tubulin, histone deacetylase 6 (HDAC6) and 20S proteasome subunits. Neuronal cytoplasmic inclusions (NCIs) were also immunopositive for these aggresome-related proteins. Double immunofluorescence staining and quantitative analysis demonstrated that the majority of GCIs contained these proteins, as well as other aggresome-related proteins, such as Hsp70, Hsp90 and 62-kDa protein/sequestosome 1 (p62/SQSTM1). Immunoelectron microscopy demonstrated immunoreactivities for γ-tubulin and HDAC6 along the fibrils comprising GCIs.


CONCLUSIONS
Our results indicate that GCIs, and probably NCIs, share at least some characteristics with aggresomes in terms of their protein components. Therefore, GCIs and NCIs may be another manifestation of aggresome-related inclusion bodies observed in neurodegenerative diseases.
Department of Pathology, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi, Japan.
Y
Y
Chiba
S
S
Takei
N
N
Kawamura
Y
Y
Kawaguchi
K
K
Sasaki
S
S
Hasegawa-Ishii
A
A
Furukawa
M
M
Hosokawa
A
A
Shimada
D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D005260:Female; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism* / Q000473:pathology; D016631:Lewy Bodies / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000378:metabolism* / Q000473:pathology; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism
D014404:Tubulin; D046988:Proteasome Endopeptidase Complex; C433811:HDAC6 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases