Related Experiment Videos
A non-human primate model for stable chronic Parkinson's disease induced by MPTP administration based on individual
Jincheol Seo1, Youngjeon Lee2, Bom Sahn Kim3
1National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, Republic of Korea; School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea.
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.
Insights
This study introduces a new method for creating stable Parkinsonian models in non-human primates using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. Adjusting MPTP dosage based on global activity (GA) ensures consistent symptom severity for Parkinson's disease research.
Area of Science:
- Neuroscience
- Primate Models
- Parkinson's Disease Research
Background:
- Reproducing stable chronic Parkinsonism in non-human primates (NHPs) using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is challenging due to a lack of objective criteria for adjusting treatment based on symptom severity.
- Existing guidelines for MPTP treatment adjustments in macaques lack specific, objective measures for individual symptom severity, hindering the development of reliable MPTP-induced chronic NHP models with consistent Parkinsonian symptoms.
Purpose of the Study:
- To develop a refined MPTP administration strategy for creating MPTP-induced Parkinson's disease (PD) models in NHPs with stable and reproducible Parkinsonian symptoms.
- To establish objective criteria for adjusting MPTP dosage based on quantifiable behavioral and physiological markers.
Main Methods:
- MPTP administration was individually adjusted based on real-time quantification of global activity (GA) using a video-based tracking system.
- A low-dose (0.2 mg/kg) intramuscular MPTP injection protocol was continuously repeated until GA decreased to below 8% of baseline levels.
- Positron emission tomography (PET) imaging was employed to monitor the longitudinal progression of Parkinsonian pathology.
Main Results:
- Significant reductions in GA and dopamine transporter (DAT) activity were observed, alongside increased Parkinsonian behavior scores, from 4 to 48 weeks post-MPTP administration.
- GA showed a strong correlation with the Parkinsonian behavior score, and DAT activity correlated with both GA and behavior scores.
- Histological analysis confirmed dopaminergic neuronal system damage in the basal ganglia, validating the model's efficacy.
Conclusions:
- The study successfully reinforced existing guidelines for producing NHP models of Parkinson's disease with stable Parkinsonian symptoms.
- This novel MPTP administration strategy, guided by global activity evaluations, represents a significant advancement in developing chronic NHP Parkinsonian models.