TY - JOUR
T1 - A quantitative approach to developing Parkinsonian monkeys (Macaca fascicularis) with intracerebroventricular 1-methyl-4-phenylpyridinium injections
AU - Li, Hao
AU - Lei, Xiaoguang
AU - Huang, Baihui
AU - Rizak, Joshua D.
AU - Yang, Lichuan
AU - Yang, Shangchuan
AU - Wu, Jing
AU - Lü, Longbao
AU - Wang, Jianhong
AU - Yan, Ting
AU - Li, Hongwei
AU - Wang, Zhengbo
AU - Hu, Yingzhou
AU - Le, Weidong
AU - Deng, Xingli
AU - Li, Jiali
AU - Xu, Lin
AU - Zhang, Baorong
AU - Hu, Xintian
N1 - Funding Information:
The authors would like to thank experimental assistants Jinpeng Gao and Huimin Xie for their kind help and Kunming Primate Research Center for technical advice and support. This work was supported by grants from National Program on Key Basic Research Project (973 Programs 2015CB755605, 2012CB825503, 2012CB825500, 2012CBA01304, 2011CB707800), the Strategic Priority Research Program of the Chinese Academy of Sciences, Grant No. XDB02010001, Selected Frontier Scientific Significant Breakthrough Project of CAS , Key Program of the Chinese Academy of Sciences ( KZCC-EW-103-2 ), Training Program of the Major Research Plan of the National Natural Science Foundation of China ( 91332120 ), National Natural Science Foundation of China ( 81471312 , 31271167 , 81271495 , 31070963 , 30921064 ), the Yunnan Provincial Project to Attract One-hundred Exceptional Talents from Overseas.
Publisher Copyright:
© 2015 Elsevier B.V.
PY - 2015/8/5
Y1 - 2015/8/5
N2 - 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.
AB - 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.
KW - Dopaminergic cell loss
KW - Intracerebroventricular administration
KW - MPP<sup>+</sup>
KW - Non-human primate animal model
KW - Parkinson's disease
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U2 - 10.1016/j.jneumeth.2015.05.008
DO - 10.1016/j.jneumeth.2015.05.008
M3 - Article
C2 - 26003862
AN - SCOPUS:84930946706
VL - 251
SP - 99
EP - 107
JO - Journal of Neuroscience Methods
JF - Journal of Neuroscience Methods
SN - 0165-0270
ER -