The Tree Shrew Model of Parkinson Disease: A Cost-Effective Alternative to Nonhuman Primate Models.

Autor:	Li H; National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Key Laboratory of Genetic Evolution & Animal Models, and National Resource Center for Nonhuman Primates, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China; Key Laboratory of Animal Models and Human Disease Mechanisms of Yunnan Province, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China., Mei L; National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Key Laboratory of Genetic Evolution & Animal Models, and National Resource Center for Nonhuman Primates, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China; Key Laboratory of Animal Models and Human Disease Mechanisms of Yunnan Province, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China; Institutes of Physical Science and Information Technology, Anhui University, Hefei, China., Nie X; Key Laboratory of Animal Models and Human Disease Mechanisms of Yunnan Province, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China., Wu L; Department of Endocrinology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China., Lv L; National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Key Laboratory of Genetic Evolution & Animal Models, and National Resource Center for Nonhuman Primates, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China; Key Laboratory of Animal Models and Human Disease Mechanisms of Yunnan Province, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China; Kunming College of Life Science, University of the Chinese Academy of Sciences, Kunming, China., Ren X; National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Key Laboratory of Genetic Evolution & Animal Models, and National Resource Center for Nonhuman Primates, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China; Key Laboratory of Animal Models and Human Disease Mechanisms of Yunnan Province, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China; Kunming College of Life Science, University of the Chinese Academy of Sciences, Kunming, China., Yang J; National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Key Laboratory of Genetic Evolution & Animal Models, and National Resource Center for Nonhuman Primates, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China; Key Laboratory of Animal Models and Human Disease Mechanisms of Yunnan Province, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China; Kunming College of Life Science, University of the Chinese Academy of Sciences, Kunming, China., Cao H; National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Key Laboratory of Genetic Evolution & Animal Models, and National Resource Center for Nonhuman Primates, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China; Key Laboratory of Animal Models and Human Disease Mechanisms of Yunnan Province, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China., Wu J; National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Key Laboratory of Genetic Evolution & Animal Models, and National Resource Center for Nonhuman Primates, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China; Key Laboratory of Animal Models and Human Disease Mechanisms of Yunnan Province, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China., Zhang Y; National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Key Laboratory of Genetic Evolution & Animal Models, and National Resource Center for Nonhuman Primates, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China; Key Laboratory of Animal Models and Human Disease Mechanisms of Yunnan Province, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China., Hu Y; National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Key Laboratory of Genetic Evolution & Animal Models, and National Resource Center for Nonhuman Primates, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China; Key Laboratory of Animal Models and Human Disease Mechanisms of Yunnan Province, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China., Wang W; National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Key Laboratory of Genetic Evolution & Animal Models, and National Resource Center for Nonhuman Primates, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China; Key Laboratory of Animal Models and Human Disease Mechanisms of Yunnan Province, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China., Turck CW; National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Key Laboratory of Genetic Evolution & Animal Models, and National Resource Center for Nonhuman Primates, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China; Key Laboratory of Animal Models and Human Disease Mechanisms of Yunnan Province, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China; Max Planck Institute of Psychiatry, Munich, Germany. Electronic address: turck@psych.mpg.de., Shi B; Department of Endocrinology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. Electronic address: shibingy@126.com., Li J; Key Laboratory of Animal Models and Human Disease Mechanisms of Yunnan Province, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China; Department of Neurology, Hackensack Meridian School of Medicine, Nutley, New Jersey. Electronic address: Jiali.li@hmhn.org., Xu L; Key Laboratory of Animal Models and Human Disease Mechanisms of Yunnan Province, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China. Electronic address: lxu@vip.163.com., Hu X; National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Key Laboratory of Genetic Evolution & Animal Models, and National Resource Center for Nonhuman Primates, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China; Key Laboratory of Animal Models and Human Disease Mechanisms of Yunnan Province, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China. Electronic address: xthu@mail.kiz.ac.cn.
Jazyk:	angličtina
Zdroj:	Laboratory investigation; a journal of technical methods and pathology [Lab Invest] 2024 Nov; Vol. 104 (11), pp. 102145. Date of Electronic Publication: 2024 Sep 27.
DOI:	10.1016/j.labinv.2024.102145
Abstrakt:	The surge in demand for experimental monkeys has led to a rapid increase in their costs. Consequently, there is a growing need for a cost-effective model of Parkinson disease (PD) that exhibits all core clinical and pathologic phenotypes. Evolutionarily, tree shrews (Tupaia belangeri) are closer to primates in comparison with rodents and could be an ideal species for modeling PD. To develop a tree shrew PD model, we used the 1-methyl-4-phenylpyridinium (MPP + ), a metabolite derived from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, to induce lesions in dopaminergic neurons of the unilateral substantia nigra. The induced tree shrew model consistently exhibited and maintained all classic clinical manifestations of PD for a 5-month period. The symptoms included bradykinesia, rest tremor, and postural instability, and ∼50% individuals showed apomorphine-induced rotations, a classic phenotype of unilateral PD models. All these are closely resembled the ones observed in PD monkeys. Meanwhile, this model was also sensitive to L-dopa treatment in a dose-dependent manner, which suggested that the motor deficits are dopamine dependent. Immunostaining showed a significant loss of dopaminergic neurons (∼95%) in the lesioned substantia nigra, which is a crucial PD pathological marker. Moreover, a control group of nigral saline injection did not show any motor deficits and pathological changes. Cytomorphologic analysis revealed that the size of nigral dopaminergic neurons in tree shrews is much bigger than that of rodents and is close to that of macaques. The morphologic similarity may be an important structural basis for the manifestation of the highly similar phenotypes between monkey and tree shrew PD models. Collectively, in this study, we have successfully developed a PD model in a small animal species that faithfully recapitulated the classic clinical symptoms and key pathological indicators of PD monkeys, providing a novel and low-cost avenue for evaluation of PD treatments and underlying mechanisms. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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