Immunohistochemical localization of aggresomal proteins in glial cytoplasmic inclusions in multiple system atrophy

Y. Chiba, S. Takei, N. Kawamura, Y. Kawaguchi, K. Sasaki, Sanae Ishii, A. Furukawa, M. Hosokawa, A. Shimada

Research output: Contribution to journalArticle

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Abstract

Aims: 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.

Original languageEnglish (US)
Pages (from-to)559-571
Number of pages13
JournalNeuropathology and Applied Neurobiology
Volume38
Issue number6
DOIs
StatePublished - Oct 1 2012

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Multiple System Atrophy
Inclusion Bodies
Neuroglia
Proteins
Synucleins
Histone Deacetylases
Immunoelectron Microscopy
Tubulin
Lewy Bodies
Lewy Body Disease
Antibodies
Oligodendroglia
Cytomegalovirus Infections
Proteasome Endopeptidase Complex
Fluorescence Microscopy
Neurodegenerative Diseases
Fluorescent Antibody Technique
Parkinson Disease

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Histology
  • Neurology
  • Clinical Neurology
  • Physiology (medical)

Cite this

Chiba, Y. ; Takei, S. ; Kawamura, N. ; Kawaguchi, Y. ; Sasaki, K. ; Ishii, Sanae ; Furukawa, A. ; Hosokawa, M. ; Shimada, A. / Immunohistochemical localization of aggresomal proteins in glial cytoplasmic inclusions in multiple system atrophy. In: Neuropathology and Applied Neurobiology. 2012 ; Vol. 38, No. 6. pp. 559-571.
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Chiba, Y, Takei, S, Kawamura, N, Kawaguchi, Y, Sasaki, K, Ishii, S, Furukawa, A, Hosokawa, M & Shimada, A 2012, 'Immunohistochemical localization of aggresomal proteins in glial cytoplasmic inclusions in multiple system atrophy', Neuropathology and Applied Neurobiology, vol. 38, no. 6, pp. 559-571. https://doi.org/10.1111/j.1365-2990.2011.01229.x

Immunohistochemical localization of aggresomal proteins in glial cytoplasmic inclusions in multiple system atrophy. / Chiba, Y.; Takei, S.; Kawamura, N.; Kawaguchi, Y.; Sasaki, K.; Ishii, Sanae; Furukawa, A.; Hosokawa, M.; Shimada, A.

In: Neuropathology and Applied Neurobiology, Vol. 38, No. 6, 01.10.2012, p. 559-571.

Research output: Contribution to journalArticle

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T1 - Immunohistochemical localization of aggresomal proteins in glial cytoplasmic inclusions in multiple system atrophy

AU - Chiba, Y.

AU - Takei, S.

AU - Kawamura, N.

AU - Kawaguchi, Y.

AU - Sasaki, K.

AU - Ishii, Sanae

AU - Furukawa, A.

AU - Hosokawa, M.

AU - Shimada, A.

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N2 - Aims: 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.

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