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

• Published in: Journal of neuroscience methods Vol. 311; pp. 277 - 287
• Main Authors: Seo, Jincheol, Lee, Youngjeon, Kim, Bom Sahn, Park, Junghyung, Yang, Sejung, Yoon, Hai-Jeon, Yoo, Jang, Park, Hyun Soo, Hong, Jung-Joo, Koo, Bon-Sang, Baek, Seung Ho, Jeon, Chang-Yeop, Huh, Jae-Won, Kim, Young-Hyun, Park, Sang Je, Won, Jinyoung, Ahn, Yu-Jin, Kim, Keonwoo, Jeong, Kang Jin, Kang, Philyong, Lee, Dong-Seok, Lim, Soo Mee, Jin, Yeung Bae, Lee, Sang-Rae
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2019
• Subjects: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine - administration & dosage; Animals; Behavior, Animal - drug effects; Brain - drug effects; Brain - metabolism; Disease Models, Animal; Dopamine Agents - administration & dosage; Female; Global activity; Macaca fascicularis; MPTP; Non-human primate; Parkinson's disease; Parkinsonian Disorders - chemically induced; Parkinsonian Disorders - physiopathology; Parkinsonian Disorders - psychology; Severity of Illness Index; Video-based tracking system; PBS; Parkinson's disease; MRI; BP; CT; PD; TH; Global activity; DAT; Video-based tracking system; Non-human primate; NHPs; GA; MPTP; PET
• ISSN: 0165-0270; 1872-678X
• DOI: 10.1016/j.jneumeth.2018.10.037

•We provide a conceptual advance of the method to produce stable Parkinsonian models.•Individual MPTP dose adjustments according to the severity of symptoms are needed.•Global activity using a video tracking system is useful in evaluating Parkinsonism.•Global activity provides an objective and accurate evaluation of symptom severity.•Global activity provides the objective criteria for adjustments of MPTP treatment. 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. 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). 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. This study reinforces previous guidelines regarding production of NHP models with stable Parkinsonian symptoms. This novel strategy of MPTP administration based on global activity evaluations provides an important conceptual advance for the development of chronic NHP Parkinsonian models.