Ultrastructure of alpha-synuclein-positive aggregations in U373 astrocytoma and rat primary glial cells.
Abnormal alpha-synuclein-positive glial cytoplasmic inclusions are found in Parkinson's disease, multiple system atrophy and dementia with Lewy bodies. We have recently developed an in vitro model of alpha-synuclein-immunoreactive aggregations in U373 astrocytoma cells. We have additionally overexpressed wild-type and a C-terminally truncated form of alpha-synuclein in primary rat glial cells. Astrocytes and oligodendrocytes were found to form alpha-synuclein-positive aggregations in vitro perinuclearly or in the processes of the cells. The morphological studies presented here demonstrate that the aggregations we have observed in vitro are not limited by a membrane but have unclear borders. They have an amorphous dense core that is intensely alpha-synuclein-immunopositive and a predominantly filamentous halo around. Mainly filamentous structures at the border area between the halo and the core are alpha-synuclein-immunoreactive. We conclude that this in vitro model of alpha-synuclein-positive glial aggregations mimics the morphology of the abnormal glial inclusions described in neurodegenerative disorders and could be a suitable model for studying their role in the pathogenesis of these diseases.
Stefanova
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N
Department of Neurology, University of lnnsbruck, Anichstrasse 35, 6020, Innsbruck, Austria.
Emgård
M
M
Klimaschewski
L
L
Wenning
G K
GK
Reindl
M
M
D000818:Animals; D001254:Astrocytoma / Q000737:chemistry / Q000473:pathology / Q000648:ultrastructure*; D018929:Cell Culture Techniques; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000473:pathology; D009457:Neuroglia / Q000737:chemistry / Q000473:pathology / Q000648:ultrastructure*; D051381:Rats; D051843:Synucleins; D014407:Tumor Cells, Cultured; D051844:alpha-Synuclein
D009419:Nerve Tissue Proteins; C497606:Snca protein, rat; D051843:Synucleins; D051844:alpha-Synuclein