Functional and neuropathological changes induced by injection of distinct alpha-synuclein strains: A pilot study in non-human primates - Inserm - Institut national de la santé et de la recherche médicale Access content directly
Journal Articles Neurobiology of Disease Year : 2023

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

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.
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Dates and versions

inserm-04033469 , version 1 (17-03-2023)

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Audrey Fayard, Alexis Fenyi, Sonia Lavisse, Sandra Dovero, Luc Bousset, et al.. Functional and neuropathological changes induced by injection of distinct alpha-synuclein strains: A pilot study in non-human primates. Neurobiology of Disease, 2023, 180, pp.106086. ⟨10.1016/j.nbd.2023.106086⟩. ⟨inserm-04033469⟩
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