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A non-human primate model for stable chronic Parkinson's disease induced by MPTP administration based on individual behavioral quantification

  • 주제(키워드) Parkinson's disease , Non-human primate , MPTP , Global activity , Video-based tracking system
  • 주제(기타) Biochemical Research Methods
  • 주제(기타) Neurosciences
  • 설명문(일반) [Seo, Jincheol; Lee, Youngjeon; Park, Junghyung; Hong, Jung-Joo; Koo, Bon-Sang; Baek, Seung Ho; Jeon, Chang-Yeop; Huh, Jae-Won; Kim, Young-Hyun; Park, Sang Je; Won, Jinyoung; Ahn, Yu-Jin; Kim, Keonwoo; Jeong, Kang Jin; Kang, Philyong; Jin, Yeung Bae; Lee, Sang-Rae] Korea Res Inst Biosci & Biotechnol, Natl Primate Res Ctr, Cheongju, South Korea; [Seo, Jincheol; Lee, Dong-Seok] Kyungpook Natl Univ, BK21 Plus KNU Creat BioRes Grp, Sch Life Sci, Daegu, South Korea; [Lee, Youngjeon; Huh, Jae-Won; Kim, Young-Hyun; Ahn, Yu-Jin; Lee, Sang-Rae] Korea Univ Sci & Technol, KRIBB Sch Biosci, Dept Funct Genom, Daejeon, South Korea; [Kim, Born Sahn; Yoon, Hai-Jeon; Yoo, Jang] Ewha Womans Univ, Dept Nucl Med, Sch Med, Seoul, South Korea; [Lim, Soo Mee] Ewha Womans Univ, Sch Med, Dept Radiol, Seoul, South Korea; [Yang, Sejung] Yonsei Univ, Dept Biomed Engn, Wonju 220710, South Korea; [Park, Hyun Soo] Seoul Natl Univ, Coll Med, Bundang Hosp, Dept Nucl Med, Seongnam, South Korea; [Kim, Keonwoo] Inje Univ, Dept Phys Therapy, Grad Sch, Gimhae, South Korea
  • 등재 SCIE, SCOPUS
  • OA유형 hybrid
  • 발행기관 ELSEVIER SCIENCE BV
  • 발행년도 2019
  • 총서유형 Journal
  • URI http://www.dcollection.net/handler/ewha/000000171885
  • 본문언어 영어
  • Published As https://dx.doi.org/10.1016/j.jneumeth.2018.10.037
  • PubMed https://pubmed.ncbi.nlm.nih.gov/30391524

초록/요약

Background: The guidelines for applying individual adjustments to macaques according to the severity of behavioral symptoms during 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment were provided to reproduce stable chronic Parkinsonism in a recent study (Potts et al., 2014). But, since there are insufficient guidelines regarding objective severity criteria of individual symptoms for adjustments of MPTP treatment, it is difficult to develop MPTP-induced chronic non-human primate (NHP) models with stable symptoms. New method: The individual adjustments of MPTP administration based on results of automatic quantification of global activity (GA) using a video-based tracking system were applied to develop MPTP-PD model. Low-dose (0.2 mg/kg) intramuscular injection was repeated continuously until GA was lower than 8% of baseline Parkinsonian behavior scores. The positron emission tomography imaging were used to follow the longitudinal course of Parkinson's disease (PD). Results: Significant reductions in GA and dopamine transporter activity, along with significant increases in Parkinsonian behavior scores were found from 4 to 48 weeks following the first administration. GA was correlated with the Parkinsonian behavior score. The dopamine transporter activity was correlated with GA and the Parkinsonian behavior score. However, it was not correlated with the total dose of MPTP. Damage of dopaminergic neuronal systems in the basal ganglia was confirmed by immunohistochemistry and Western blot. Comparison with existing method: This study reinforces previous guidelines regarding production of NHP models with stable Parkinsonian symptoms. Conclusions: This novel strategy of MPTP administration based on global activity evaluations provides an important conceptual advance for the development of chronic NHP Parkinsonian models.

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