Lab Anim Res.  2019 Aug;35(2):61-69. 10.1186/s42826-019-0012-2.

Comparative analysis of dose-dependent neurotoxic response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in C57BL/6 N mice derived from three different sources

Affiliations
  • 1Exercise Biochemistry Laboratory, Korea National Sport University, Seoul 05541, South Korea. chojy86@knsu.ac.kr
  • 2Department of Microbiology and Immunology, INJE University College of Medicine, Busan 47392, South Korea.
  • 3College of Veterinary Medicine, Kyungpook National University, Daegu 41566, South Korea.
  • 4College of Pharmacy, Pusan National University, Busan 46241, South Korea.
  • 5Department of Biomaterials Science, College of Natural Resources & Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang 50463, South Korea.

Abstract

MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine is commonly used to induce nigrostriatal defects to induce parkinsonism and/or parkinsonian syndrome, to replicate the lesions seen in Parkinson's disease (PD), with use in numerous PD models in mice. It has been suggested that various biological characteristics including strain could result in differing mortality rates, sensitivity to MPTP administration, and reproducibility of lesions in mice, but there is no evidence on the sensitivity of C57BL/6 mice from different origins to MPTP and its associated pathological lesions. In this study, we investigated the magnitude of the dose-dependent response to acute MPTP administration in C57BL/6NKorl mice and two commercialized C57BL/6 stocks derived from the United States and Japan. We measured biological features (body weight, temperature, and composition), nigrostriatal neurotoxic responses (dopamine levels, tyrosine hydroxylase enzymes, and protein carbonylation) and motor function. In results, the three different C57BL/6 stocks exhibited similar overall neurotoxic response and locomotor impairment which increased in a dose-dependent manner with acute MPTP administration (10 mg/kg, 20 mg/kg, and 30 mg/kg, all with external heat support), although some of these differences were not significant. In conclusion, this study provides scientific evidence that C57BL/6NKorl mice can be used as an alternative animal model for practical and targeted PD research.

Keyword

Parkinson's disease; MPTP; 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; C57BL/6Nkorl; Mouse stock

MeSH Terms

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine*
Animals
Hot Temperature
Japan
Mice*
Models, Animal
Mortality
Parkinson Disease
Parkinsonian Disorders
Population Characteristics
Tyrosine 3-Monooxygenase
United States
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Tyrosine 3-Monooxygenase
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