Alpha-synuclein is highly prone to distribution in the hippocampus and midbrain in tree shrews, and its fibrils seed Lewy body-like pathology in primary neurons.

Abstract

The Chinese tree shrew (TS) has many unique advantages that make it suitable for use as an experimental animal model for human disease including moderate body size, low cost of feeding, short reproductive cycle and lifespan, and close phylogenetic relationship to primates. Our previous studies have shown that TS treated with the mitochondrial inhibitor MPTP displayed classic Parkinsonian symptoms. Additionally, the structure of TS alpha-synuclein (α-syn) is highly homologous to that found in humans. Previous studies have concluded that misfolded, fibrillar α-syn is a hallmark of α-synucleinopathies. In this study, we examined the distribution and expression levels of α-syn in different TS brain regions. We also obtained recombinant TS α-syn protein to study its aggregation and cytotoxic properties in primary neurons. Our results showed that α-syn was expressed in numerous different brain regions in TS but was most abundant in the hippocampus and midbrain. The recombinant α-syn of TS displayed straight fibrils when incubated for 72 h in vitro, which is very similar to human α-syn. When exposed to primary neurons, the TS and human α-syn fibrils led to cytotoxicity and Lewy-like pathology. Our findings indicated that TS could be a potential animal model to study the pathology of α-synucleinopathies.