Ultrastructure of α-synuclein-positive aggregations in U373 astrocytoma and rat primary glial cells

Abstract

Abnormal α-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 α-synuclein-immunoreactive aggregations in U373 astrocytoma cells. We have additionally overexpressed wild-type and a C-terminally truncated form of α-synuclein in primary rat glial cells. Astrocytes and oligodendrocytes were found to form α-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 α-synuclein-immunopositive and a predominantly filamentous halo around. Mainly filamentous structures at the border area between the halo and the core are α-synuclein-immunoreactive. We conclude that this in vitro model of α-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.