title: 1-Methyl-4-phenylpyridinium stereotactic infusion completely and specifically ablated the nigrostriatal dopaminergic pathway in rhesus macaque.
abstract: BACKGROUND
  Complete and specific ablation of a single dopaminergic (DA) pathway is a critical step to distinguish the roles of DA pathways in vivo. However, this kind of technique has not been reported in non-human primates. This study aimed to establish a lesioning method with a complete and specific ablation.
  
  
  METHODS
  A carefully designed infusion route based on a MRI stereotactic technique was developed to deliver the highly selective dopaminergic toxin 1-methyl-4-phenylpyridinium (MPP+) unilaterally into multiple sites of compact part of substantia nigra (SNc) and striatum in monkeys. The nigrostriatal DA pathway was selected because lesioning of this pathway may induce symptoms that are suitable for evaluation. The pathological, behavioral, neuropharmacological, and clinical laboratorial data were collected to evaluate the lesioning effects.
  
  
  RESULTS
  Pathological examination revealed a complete ablation of tyrosine hydroxylase positive (TH+) neurons in the SNc, while preserving intact TH+ neurons in the ventral tegmental area (VTA) nearby. TH+ projections in the striatum were also unilaterally lost. The monkeys displayed stable (>28 weeks) rotations and symptoms which were expected with loss of DA neurons in the SNc, with rest tremor being an exception. No item implied the presence of a severe side effect caused by the operation or the intracerebral MPP+ infusion. The results suggested that rest tremor may not directly rely on the nigrostriatal pathway.
  
  
  CONCLUSIONS
  Taken together, in addition to providing a specific nigrostriatal DA lesioned model, this method, combined with brain stimulation or other techniques, can be applied as a powerful tool for the complete lesion of any desired DA pathway in order to study its specific functions in the brain.
authors.affiliation: Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 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, Yunnan, China; University of the Chinese Academy of Sciences, Beijing, China.
authors.forename: Hao
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, Yunnan, China; University of the Chinese Academy of Sciences, Beijing, 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, Yunnan, China.
authors.forename: Joshua
authors.initials: J
authors.lastname: Rizak
authors.affiliation: Medical Imaging Department, Kunming General Hospital of PLA, Kunming, Yunnan, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.affiliation: Medical Imaging Department, Kunming General Hospital of PLA, Kunming, Yunnan, China.
authors.forename: Liqi
authors.initials: L
authors.lastname: Xu
authors.affiliation: Yunnan Key Laboratory of Primate Biomedical Research, Kunming, Yunnan, China.
authors.forename: Tianzhuang
authors.initials: T
authors.lastname: Huang
authors.affiliation: Medical Imaging Department, Kunming General Hospital of PLA, Kunming, Yunnan, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
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, 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, 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, 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, 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, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Le
authors.affiliation: Neurosurgery Department, 1st Affiliated Hospital of Kunming Medical University, Kunming, 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, 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, Yunnan, China; CAS Center for Excellence in Brain Science, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Yao
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, Yunnan, China; CAS Center for Excellence in Brain Science, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
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, Yunnan, China; CAS Center for Excellence in Brain Science, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Xintian
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Baorong
authors.initials: B
authors.lastname: Zhang
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001522:Behavior, Animal; D001835:Body Weight / Q000187:drug effects; D002452:Cell Count; D003342:Corpus Striatum / Q000473:pathology; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000473:pathology*; D006403:Hematologic Tests; D008253:Macaca mulatta; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000473:pathology*; D010300:Parkinson Disease / Q000097:blood / Q000188:drug therapy; D012119:Respiration / Q000187:drug effects; D012399:Rotation; D013238:Stereotaxic Techniques; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D014446:Tyrosine 3-Monooxygenase; D015655:1-Methyl-4-phenylpyridinium