A non-human primate model for stable chronic Parkinson’s disease induced by MPTP administration based on individual behavioral quantification = 활동량의 변화를 기준으로 개체별 MPTP를 차등 투여해 원숭이 만성 파킨슨병 모델 개발 및 검증

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Title
A non-human primate model for stable chronic Parkinson’s disease induced by MPTP administration based on individual behavioral quantification = 활동량의 변화를 기준으로 개체별 MPTP를 차등 투여해 원숭이 만성 파킨슨병 모델 개발 및 검증
Author(s)
Jincheol Seo; Youngjeon Lee; B S Kim; Junghyung Park; S Yang; H J Yoon; J Yoo; H S Park; Jung Joo HongBon Sang KooSeung Ho BaekChang Yeop JeonJae Won HuhYoung-Hyun KimSang Je Park; Jinyoung Won; Yu Jin Ahn; Keonwoo Kim; Kang Jin JeongPhilyong Kang; D S Lee; S M Lim; Yeung Bae Jin; Sang-Rae Lee
Bibliographic Citation
Journal of Neuroscience Methods, vol. 311, pp. 277-287
Publication Year
2019
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.
Keyword
Global activityMPTPNon-human primateParkinson's diseaseVideo-based tracking system
ISSN
0165-0270
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.jneumeth.2018.10.037
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of National Bio-Infrastructure > National Primate Research Center > 1. Journal Articles
Ochang Branch Institute > Division of National Bio-Infrastructure > Futuristic Animal Resource & Research Center > 1. Journal Articles
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