title: A quantitative approach to developing Parkinsonian monkeys (Macaca fascicularis) with intracerebroventricular 1-methyl-4-phenylpyridinium injections.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  We developed Parkinsonian monkeys within controlled time frames by regulating the accumulated dose of MPP(+) intracerebroventricular administered, while limiting side effects often witnessed in models developed with the peripheral administration of MPTP, makes this model highly suitable for treatment development.
  
  
  CONCLUSIONS
  This novel approach provides an edge in evaluating the mechanisms of PD pathology associated with environmental toxins and novel treatment approaches as the formula developed provides a "map" to control and predict the modeling processes.
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China; University of the Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang, China.
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Lei
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China; University of the Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Baihui
authors.initials: B
authors.lastname: Huang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Rizak
authors.affiliation: School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, Yunnan, China.
authors.forename: Lichuan
authors.initials: L
authors.lastname: Yang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China.
authors.forename: Shangchuan
authors.initials: S
authors.lastname: Yang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Kunming Primate Research Center, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China.
authors.forename: Longbao
authors.initials: L
authors.lastname: Lü
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Yan
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Li
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China.
authors.forename: Zhengbo
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China.
authors.forename: Yingzhou
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Le
authors.affiliation: Neurosurgery Department, 1st Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan, China.
authors.forename: Xingli
authors.initials: X
authors.lastname: Deng
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China.
authors.forename: Jiali
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China; CAS Center for Excellence in Brain Science, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang, China. Electronic address: brzhang@zju.edu.cn.
authors.forename: Baorong
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China; CAS Center for Excellence in Brain Science, Chinese Academy of Sciences, Shanghai 200031, China; Kunming Primate Research Center, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China. Electronic address: xthu@mail.kiz.ac.cn.
authors.forename: Xintian
authors.initials: X
authors.lastname: Hu
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005684:Gait / Q000187:drug effects / Q000502:physiology; D006540:Herbicides / Q000633:toxicity*; D007276:Injections, Intraventricular / Q000379:methods; D008252:Macaca fascicularis; D008297:Male; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000175:diagnosis / Q000503:physiopathology; D004856:Postural Balance / Q000187:drug effects / Q000502:physiology; D012720:Severity of Illness Index; D013997:Time Factors; D014202:Tremor / Q000175:diagnosis / Q000209:etiology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D006540:Herbicides; D014446:Tyrosine 3-Monooxygenase; D015655:1-Methyl-4-phenylpyridinium
keywords: Dopaminergic cell loss; Intracerebroventricular administration; MPP(+); Non-human primate animal model; Parkinson's disease