Parkinson's disease (PD) is one of the most common neurodegenerative diseases, but its pathogenesis is still unclear. Recently a new approach has been used to develop Parkinsonian monkeys with unilateral intracerebroventricular injections of 1-methyl-4-phenylpyridinium ion (MPP). However, this new method still has some shortcomings, which limits the potential application of MPTP-induced PD monkey models. In the present study, we aimed to develop a modified protocol to induce chronic Parkinsonian non-human primate model with low-dose MPP by bilateral intracerebroventricular injections. The induced time of PD model, model stability, phenotypes and Tc-TRODAT-1 single-photon emission computed tomography (SPECT) brain imaging of dopamine transporter were compared between unilateral and bilateral modeling groups. The results showed that PD symptoms in the bilateral modeling group were induced earlier, more serious, and lasted longer after the administration stage, compared with those of the unilateral modeling group. In the unilateral modeling group, radioactive uptake of the striatum was decreased significantly in the left side (MPP injected side), but unaffected in the right side. While in the bilateral modeling group, the radioactive uptake of the bilateral striatum was declined dramatically and symmetrically. These results suggest that bilateral intracerebroventricular injection of MPP is superior to unilateral intracerebroventricular injection in establishing chronic Parkinsonian non-human primate model and may supply a better animal model for PD research.

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