A quantitative approach to developing Parkinsonian monkeys (Macaca fascicularis) with intracerebroventricular 1-methyl-4-phenylpyridinium injections

Hao Li, Xiaoguang Lei, Baihui Huang, Joshua D. Rizak, Lichuan Yang, Shangchuan Yang, Jing Wu, Longbao Lü, Jianhong Wang, Ting Yan, Hongwei Li, Zhengbo Wang, Yingzhou Hu, Weidong Le, Xingli Deng, Jiali Li, Lin Xu, Baorong Zhang, Xintian Hu

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Background: Non-human primate Parkinson's disease (PD) models are essential for PD research. The most extensively used PD monkey models are induced with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). However, the modeling processes of developing PD monkeys cannot be quantitatively controlled with MPTP. Therefore, a new approach to quantitatively develop chronic PD monkey models will help to advance the goals of "reduction, replacement and refinement" in animal experiments. New method: A novel chronic PD monkey models was reported using the intracerebroventricular administration of 1-methyl-4-phenylpyridinium (MPP+) in Cynomolgus monkeys (Macaca fascicularis). Results: This approach successfully produced stable and consistent PD monkeys with typical motor symptoms and pathological changes. More importantly, a sigmoidal relationship (Y=8.15801e-0.245/x; R=0.73) was discovered between PD score (Y) and cumulative dose of MPP+ (X). This relationship was then used to develop two additional PD monkeys under a specific time schedule (4 weeks), with planned PD scores (7) by controlling the dose and frequency of the MPP+ administration as an independent validation of the formula.

Original languageEnglish (US)
Pages (from-to)99-107
Number of pages9
JournalJournal of Neuroscience Methods
Volume251
DOIs
StatePublished - Aug 5 2015

Keywords

  • Dopaminergic cell loss
  • Intracerebroventricular administration
  • MPP<sup>+</sup>
  • Non-human primate animal model
  • Parkinson's disease

ASJC Scopus subject areas

  • Neuroscience(all)

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