• Jincheol Seo, Youngjeon Lee, Bom Sahn Kim, Junghyung Park, Sejung Yang, Hai-Jeon Yoon, Jang Yoo, Hyun Soo Park, Jung-Joo Hong, Bon-Sang Koo, Seung Ho Baek, Chang-Yeop Jeon, Jae-Won Huh, Young-Hyun Kim, Sang Je Park, Jinyoung Won, Yu-Jin Ahn, Keonwoo Kim, Kang Jin Jeong, Philyong Kang, Dong-Seok Lee, Soo Mee Lim, Yeung Bae Jin, and Sang-Rae Lee.
• National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, Republic of Korea; School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea.
• J. Neurosci. Methods. 2019 Jan 1; 311: 277-287.

BackgroundThe guidelines for applying individual adjustments to macaques according to the severity of behavioral symptoms during 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment were provided to reproduce stable chronic Parkinsonism in a recent study (Potts et al., 2014). But, since there are insufficient guidelines regarding objective severity criteria of individual symptoms for adjustments of MPTP treatment, it is difficult to develop MPTP-induced chronic non-human primate (NHP) models with stable symptoms.New MethodThe individual adjustments of MPTP administration based on results of automatic quantification of global activity (GA) using a video-based tracking system were applied to develop MPTP-PD model. Low-dose (0.2 mg/kg) intramuscular injection was repeated continuously until GA was lower than 8% of baseline Parkinsonian behavior scores. The positron emission tomography imaging were used to follow the longitudinal course of Parkinson's disease (PD).ResultsSignificant reductions in GA and dopamine transporter activity, along with significant increases in Parkinsonian behavior scores were found from 4 to 48 weeks following the first administration. GA was correlated with the Parkinsonian behavior score. The dopamine transporter activity was correlated with GA and the Parkinsonian behavior score. However, it was not correlated with the total dose of MPTP. Damage of dopaminergic neuronal systems in the basal ganglia was confirmed by immunohistochemistry and Western blot.Comparison With Existing MethodThis study reinforces previous guidelines regarding production of NHP models with stable Parkinsonian symptoms.ConclusionsThis novel strategy of MPTP administration based on global activity evaluations provides an important conceptual advance for the development of chronic NHP Parkinsonian models.Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

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