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Sudden cardiac death as a naturally-occurring ventricular hypertrophy in Macaca fascicularis
Hyeon-Gu Yeo,Junghyung Park,Hyun Kuk Kim,Joo Myung Lee,Bon-Sang Koo,Jeong-Hee An,Chang-Yeop Jeon,You Jung An,Won Seok Choi,Sung-Hyun Park,Jincheol Seo,Jinyoung Won,Keonwoo Kim,Jiyeon Cho,Yu Gyeong Kim 충북대학교 동물의학연구소 2021 Journal of Biomedical and Translational Research Vol.22 No.3
Seo, Jincheol,Lee, Youngjeon,Kim, Bom Sahn,Park, Junghyung,Yang, Sejung,Yoon, Hai-Jeon,Yoo, Jang,Park, Hyun Soo,Hong, Jung-Joo,Koo, Bon-Sang,Baek, Seung Ho,Jeon, Chang-Yeop,Huh, Jae-Won,Kim, Young-Hyu Elsevier 2019 Journal of neuroscience methods Vol.311 No.-
<P><B>Abstract</B></P> <P><B>Background</B></P> <P>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.</P> <P><B>New method</B></P> <P>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).</P> <P><B>Results</B></P> <P>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.</P> <P><B>Comparison with existing method</B></P> <P>This study reinforces previous guidelines regarding production of NHP models with stable Parkinsonian symptoms.</P> <P><B>Conclusions</B></P> <P>This novel strategy of MPTP administration based on global activity evaluations provides an important conceptual advance for the development of chronic NHP Parkinsonian models.</P> <P><B>Highlights</B></P> <P> <UL> <LI> We provide a conceptual advance of the method to produce stable Parkinsonian models. </LI> <LI> Individual MPTP dose adjustments according to the severity of symptoms are needed. </LI> <LI> Global activity using a video tracking system is useful in evaluating Parkinsonism. </LI> <LI> Global activity provides an objective and accurate evaluation of symptom severity. </LI> <LI> Global activity provides the objective criteria for adjustments of MPTP treatment. </LI> </UL> </P>