Abstract
Objective: This study aimed to investigate the contribution of CD3 epsilon (e) 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 e 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-e-epitope expression, the immunohistochemical study and the quantitative statistical analysis between the areas of CD3-e-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 e epitope. Both the immunohistochemical study and the quantitative statistical analysis revealed that the areas positive for CD3 e 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 e 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-e-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 e epitope.
Highlights
The pathogenesis of Multiple System Atrophy (MSA) currently remains unknown
This study aimed to investigate the contribution of Cluster of Differentiation 3 (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)
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
Summary
The pathogenesis of Multiple System Atrophy (MSA) currently remains unknown. MSA is a single entity that includes olivopontocerebellar atrophy (OPCA), striatonigral degeneration (SND) and Shy-Drager syndrome [1]. One type of MSA is characterized by damage mainly to cerebellum, especially cerebellar Purkinje cells, and this type is designated as Multiple System Atrophy-Cerebellar type (MSA-C) [2]. Neuropathological findings in cases of MSA-C show the loss of Purkinje cells in the cerebellar cortex, and do their numbers decrease, but abnormal morphological changes of Purkinje cells occur as part of the process of degeneration under MSA-C stress [1]. Golgi impregnation method has often been used in the study of morphological alterations of cerebellar Purkinje cells from earlier studies [2]. Golgi impregnation method itself includes the complexity of staining and its lack of accurate reproducibility. A number of molecular markers for the morphological and functional analysis of cerebellar Purkinje cells have already been reported [3]-[13]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
