Objective: To investigate the Lewy-body-induced degeneration and synucleopathy in wild-type mice while focusing upon origin of the Lewy bodies.

Background: Neurodegenerative diseases, such as Parkinson’s disease, multiple system atrophy or dementia with Lewy bodies (LB) are characterized by accumulation of misfolded α-synuclein proteins. Cell to cell spreading of misfolded proteins may be considered as a hallmark in Prion-like diseases.

Method: Using disease-speci!c aggregates, extracted from patient’s post-mortem brains, the PRIPRO project aimed at elucidating the cellular commonalities and speci!cities, as well as temporo-spatial development of each pathology. The !rst part of this project was dedicated to the evaluation of the toxicity of LB extracts collected from di”erent patients (patient-specific) or different brain regions (brain structure-specific), injected stereotactically into the substantia nigra of wild-type mice. The second part of the PRIPRO project aimed at assessing the infectious nature of these pathological inclusions, using parabiotic pairing of wild-type mice.

Results: In both experiments, animals were sacri!ced 4 months after stereotaxic surgery. Their brains were !xed and processed for immune-histological analysis. Similarities and differences between the pathologic triggers are evaluated in relation to: (i) the extent of the induced lesion in the nigrostriatal pathway, and (ii) the extent of synucleinopathy, focusing notably on phosphorylated-α-synuclein at Ser129.

Conclusion: Our results suggest that Lewy Bodies collected from di”erent brain areas do not yield the same extent of neurodegeneration, thus calling for a thorough differential characterization of the speci!c synuclein species present in post-mortem extracts collected from different patients and different brain regions.

« Back to MDS Virtual Congress 2020

MDS Abstracts - https://www.mdsabstracts.org/abstract/characterization-of-lewy-bodies-induced-neurodegeneration-and-synucleopathy-in-wild-type-mice/