A non-human primate model for stable chronic Parkinson's disease induced by MPTP administration based on individual behavioral quantification

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 KangDong Seok Lee, Soo Mee Lim, Yeung Bae Jin, Sang Rae Lee

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Background: The 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 method: The 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). Results: Significant 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 method: This study reinforces previous guidelines regarding production of NHP models with stable Parkinsonian symptoms. Conclusions: This novel strategy of MPTP administration based on global activity evaluations provides an important conceptual advance for the development of chronic NHP Parkinsonian models.

Original languageEnglish
Pages (from-to)277-287
Number of pages11
JournalJournal of Neuroscience Methods
Volume311
DOIs
StatePublished - 1 Jan 2019

Keywords

  • Global activity
  • MPTP
  • Non-human primate
  • Parkinson's disease
  • Video-based tracking system

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