Tissue Eng Regen Med.  2016 Feb;13(1):100-109. 10.1007/s13770-015-0106-3.

Behavior, PET and Histology in Novel Regimen of MPTP Marmoset Model of Parkinson's Disease for Long-Term Stem Cell Therapy

• Yun JW
• Ahn JB
• Kwon E
• Ahn JH
• Park HW
• Heo H
• Park JS
• Kim H
• Paek SH
• Kang BC

• KMID: 2360872
• DOI: http://doi.org/10.1007/s13770-015-0106-3

Abstract

Stem cell technologies are particularly attractive in Parkinson's disease (PD) research although they occasionally need long-term treatment for anti-parkinsonian activity. Unfortunately, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) widely used as a model for PD has several limitations, including the risk of dose-dependent mortality and the difficulty of maintenance of PD symptoms during the whole experiment period. Therefore, we tested if our novel MPTP regimen protocol (2 mg/kg for 2 consecutive days and 1 mg/kg for next 3 consecutive days) can be maintained stable parkinsonism without mortality for long-term stem cell therapy. For this, we used small-bodied common marmoset monkeys (Callithrix jacchus) among several nonhuman primates showing high anatomical, functional, and behavioral similarities to humans. Along with no mortality, the behavioral changes involved in PD symptoms were maintained for 32 weeks. Also, the loss of jumping ability of the MPTP-treated marmosets in the Tower test was not recovered by 32 weeks. Positron emission tomography (PET) analysis revealed that remarkable decreases of bindings of ¹â¸F-FP-CIT were observed at the striatum of the brains of the marmosets received MPTP during the full period of the experiment for 32 weeks. In the substantia nigra of the marmosets, the loss of tyrosine hydroxylase (TH) immunoreactivity was also observed at 32 weeks following the MPTP treatment. In conclusion, our low-dose MPTP regimen protocol was found to be stable parkinsonism without mortality as evidenced by behavior, PET, and TH immunohistochemistry. This result will be useful for evaluation of possible long-term stem cell therapy for anti-parkinsonian activity.

Keyword

Animal model; Marmoset; Nonhuman primate; Parkinson's disease; 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

MeSH Terms

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine*
Brain
Callithrix*
Haplorhini
Humans
Immunohistochemistry
Models, Animal
Mortality
Parkinson Disease*
Parkinsonian Disorders
Positron-Emission Tomography
Primates
Stem Cells*
Substantia Nigra
Tyrosine 3-Monooxygenase
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Tyrosine 3-Monooxygenase