{Reference Type}: Journal Article
{Title}: Functional and neuropathological changes induced by injection of distinct alpha-synuclein strains: A pilot study in non-human primates.
{Author}: Fayard A;Fenyi A;Lavisse S;Dovero S;Bousset L;Bellande T;Lecourtois S;Jouy C;Guillermier M;Jan C;Gipchtein P;Dehay B;Bezard E;Melki R;Hantraye P;Aron Badin R;
{Journal}: Neurobiol Dis
{Volume}: 180
{Issue}: 0
{Year}: 05 2023 16
{Factor}: 7.046
{DOI}: 10.1016/j.nbd.2023.106086
{Abstract}: The role of alpha-synuclein in Parkinson's disease has been heavily investigated since its discovery as a component of Lewy bodies. Recent rodent data demonstrate that alpha-synuclein strain structure is critical for differential propagation and toxicity. Based on these findings, we have compared, for the first time, in this pilot study, the capacity of two alpha-synuclein strains and patient-derived Lewy body extracts to model synucleinopathies after intra-putaminal injection in the non-human primate brain. Functional alterations triggered by these injections were evaluated in vivo using glucose positron emission tomography imaging. Post-mortem immunohistochemical and biochemical analyses were used to detect neuropathological alterations in the dopaminergic system and alpha-synuclein pathology propagation. In vivo results revealed a decrease in glucose metabolism more pronounced in alpha-synuclein strain-injected animals. Histology showed a decreased number of dopaminergic tyrosine hydroxylase-positive cells in the substantia nigra to different extents according to the inoculum used. Biochemistry revealed that alpha-synuclein-induced aggregation, phosphorylation, and propagation in different brain regions are strain-specific. Our findings show that distinct alpha-synuclein strains can induce specific patterns of synucleinopathy in the non-human primate, changes in the nigrostriatal pathway, and functional alterations that resemble early-stage Parkinson's disease.