Objective: Recent studies have revealed that intracerebral injection of synthetic α-synuclein (α-syn) fibrils into olfactory bulb (OB) of mice induced prion-like propagation of α-syn aggregates pathology. Here we sought to reveal the propagation fashion in non-human primates (NHP).

Background: Parkinson’s disease (PD) is the neurodegenerative disease characterized by α-synuclein (α-syn) aggregates, called Lewy bodies. The α-syn aggregates are believed to propagate in brains in a prion-like fashion via two major pathways: the olfactory and vagal pathways. Recently, the common marmoset (Callithrix jacchus) has gathered a lot of attention in the field of neuroscience because of its useful characteristics as a non-human primate model. In this study, we inoculated α-syn fibrils in the olfactory bulb of a common marmoset and analyzed its pathological progression.

Methods: Recombinant full-length marmoset α-syn was purified and incubated with agitation for a week to generate α-syn fibrils. A two-year-old female common marmoset was anesthetized with ketamine and isoflurane/oxygen mixture. Then, 0.8ul of fibrils solution (4mg/ml in sterile PBS) was stereotaxically injected using glass capillary at two sites in the unilateral olfactory bulb (OB). Three months after α-syn fibrils injection, the marmoset was sacrificed and perfused with PBS followed by 4% PFA in PBS. Eight-μm coronal sections were made and immunostained using phosphorylated α-syn (p-α-syn), anti-ubiquitin (Ub) and anti-p62 antibodies.

Results: Widespread p-α-syn positive cells were observed in the ipsilateral OB, piriform cortex and amygdala, suggesting the spreading along with anatomically connected neurons. These pre-Lewy body-like aggregation were also positive for Ub and p62. Importantly, we observed very few p-α-syn pathology in the contralateral side. In addition, Mn-contrasted magnetic resonance imaging (MRI) revealed mild atrophy of ipsilateral OB.

Conclusions: We created a new non-human primate PD model triggered in olfactory bulb.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/%ce%b1-synuclein-propagation-via-olfactory-pathway-in-non-human-primate-model/