Functional and neuropathological changes induced by injection of distinct alpha-synuclein strains: A pilot study in non-human primates

• DOI: 10.1016/j.nbd.2023.106086
• Publication Date: 2023-03-17T02:00:22Z
• Authors: Audrey Fayard; Alexis Fenyi; Sonia Lavisse; Sandra Dovero; Luc Bousset; Tracy Bellande; Sophie Lecourtois; Christophe Jouy; Martine Guillermier; Caroline Jan; Pauline Gipchtein; Benjamin Dehay; Erwan Bezard; Ronald Melki; Philippe Hantraye; Romina Aron Badin
• Keywords: Synucleinopathies; Human brain; Lewy body; Alpha (finance)

The role of alpha-synuclein in Parkinson's disease has been heavily investigated since its discovery as a component Lewy bodies. Recent rodent data demonstrate that strain structure is critical for differential propagation and toxicity. Based on these findings, we have compared, the first time, this pilot study, capacity two strains patient-derived body extracts to model synucleinopathies after intra-putaminal injection non-human primate brain. Functional alterations triggered by injections were evaluated vivo using glucose positron emission tomography imaging. Post-mortem immunohistochemical biochemical analyses used detect neuropathological dopaminergic system pathology propagation. In results revealed decrease metabolism more pronounced strain-injected animals. Histology showed decreased number tyrosine hydroxylase-positive cells substantia nigra different extents according inoculum used. Biochemistry alpha-synuclein-induced aggregation, phosphorylation, brain regions are strain-specific. Our findings show distinct can induce specific patterns synucleinopathy primate, changes nigrostriatal pathway, functional resemble early-stage disease.