TITLE:
Contribution of CD3 ε Epitope and Oxidative Type of Copper-Zinc Superoxide Dismutase to the Degeneration Processes of Cerebellar Purkinje Cells in Patients with Multiple System Atrophy-Cerebellar Type (MSA-C: Olivopontocerebellar Atrophy, OPCA): An Immunohistochemical Study
AUTHORS:
Masako Kato, Shinsuke Kato, Kiyota Kato, Kazuhiko Hayashi
KEYWORDS:
CD3 Epsilon (ε) Epitope, Glial Cytoplasmic Inclusion (GCI), Multiple System Atrophy, Oxidative Stress, Purkinje Cell
JOURNAL NAME:
World Journal of Neuroscience,
Vol.6 No.4,
November
24,
2016
ABSTRACT: Objective: This study aimed to investigate the
contribution of CD3 epsilon (ε)
epitope and oxidative type of copper-zinc superoxide dismutase to the
degeneration processes of cerebellar Purkinje cells in patients with Multiple
System Atrophy-Cerebellar type (MSA-C). Methods: This retrospective study was
carried out on autopsy specimens of 17 patients with sporadic MSA-C and 10 normal
individuals. Paraffin sections of autopsied cerebella and pontes were immunostained
with polyclonal antibodies against CD3 ε epitope and oxidative modification to cysteine sulfonic acid of cys111 in human copper-zinc
superoxide dismutase (Ox-SOD1). With respect to the areas of CD3-ε-epitope expression, the
immunohistochemical study and the quantitative statistical analysis between the
areas of CD3-ε-epitope expression in
the surviving Purkinje cells of MSA-C patients and their disease duration were
performed. Results: The cell bodies and dendritic arborization including
primary, secondary, and tertiary dendrites of normal Purkinje cells were
intensely immunostained by the antibody against CD3 ε epitope. Both the immunohistochemical study and the quantitative
statistical analysis revealed that the areas positive for CD3 ε epitope disappeared in the order from
tertiary dendrites, secondary dendrites, primary dendrites toward the cell
bodies, along with the disease progression. In addition, Glial Cytoplasmic
Inclusions (GCIs) and Neuronal Cytoplasmic Inclusions (NCIs) were strongly
positive for CD3 ε epitope. The surviving
Purkinje cells in MSA-C showed immunostaining by the anti-Ox-SOD1 antibody,
although normal Purkinje cells did not. Conclusion: Based on the oxidative
stress that the surviving Purkinje cells in MSA-C express Ox-SOD1, the functions
of morphogenesis and morphological maintenance related to CD3-ε-epitope expression of the MSA-C
Purkinje cells are impaired from the peripheral dendrites toward the cell bodies
as the center of the Purkinje cell system. In addition, GCIs and NCIs that are
pathological hallmarks of MSA also intensely express CD3 ε epitope.