Objective: The aim of this study was to investigate, in wild-type mice, the spreading and neurodegeneration induced by intracerebral injection of structurally well-defined α-synuclein assemblies (ribbons and fibrils), previously shown efficient in α-synuclein-overexpressing rats (Peerlaerts et al, 2015).

Background: Aggregation of α-synuclein is implicated in several neurodegenerative diseases. Emerging evidence have strongly implicated cell-to-cell transmission of misfolded α-synuclein as a pathogenetic mechanism in synucleinopathies. Several experimental paradigms have been used to study α-synuclein propagation in animals, in particular injections of exogenous in vitro-generated preformed α-synuclein assemblies (Bousset et al., 2013) or α-synuclein containing Lewy Bodies (LB) extracts from postmortem PD patient brain tissue (Recasens et al., 2014).

Methods: Wild-type mice received a stereotactic injection in the substantia nigra of synthetic α-synuclein ribbons and fibrils at various concentrations. Four months after injection, extensive analysis was performed to assess qualitatively, quantitatively and spatially in the whole brain the extent and pattern of lesion as well as the occurrence of synucleinopathy using both biochemical and histochemical procedures.

Results: Although no nigrostriatal degeneration was achieved, we observed a modest immunopositive signal for α-synuclein serine 129 phosphorylation, suggestive of an ongoing pathological process.

Conclusions: This study suggests that wild-type animals are less prone to develop α-synuclein pathology than overexpressing animals and might require a longer survival time to develop a full pathology.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/assessment-of-neurodegeneration-and-spreading-of-%ce%b1-synuclein-pathology-induced-by-structurally-defined-%ce%b1-synuclein-assemblies-in-wild-type-mice/