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

Title
A non-human primate model for stable chronic Parkinson's disease induced by MPTP administration based on individual behavioral quantification
Authors
Seo J.Lee Y.Kim B.S.Park J.Yang S.Yoon H.-J.Yoo J.Park H.S.Hong J.-J.Koo B.-S.Baek S.H.Jeon C.-Y.Huh J.-W.Kim Y.-H.Park S.J.Won J.Ahn Y.-J.Kim K.Jeong K.J.Kang P.Lee D.-S.Lim S.M.Jin Y.B.Lee S.-R.
Ewha Authors
임수미윤혜전
SCOPUS Author ID
임수미scopus; 윤혜전scopus
Issue Date
2019
Journal Title
Journal of Neuroscience Methods
ISSN
0165-0270JCR Link
Citation
Journal of Neuroscience Methods vol. 311, pp. 277 - 287
Keywords
Global activityMPTPNon-human primateParkinson's diseaseVideo-based tracking system
Publisher
Elsevier B.V.
Indexed
SCI; SCIE; SCOPUS WOS scopus
Document Type
Article
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. © 2018 The Authors
DOI
10.1016/j.jneumeth.2018.10.037
Appears in Collections:
의과대학 > 의학과 > Journal papers
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