2022, Vol. 26 ›› Issue (8): 1247-1252
Comparison and evaluation of MPTP-induced subacute and chronic models of Parkinson’s disease in mice
A mouse model of Parkinson's disease that is inducted by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is one of the widely used animal models that partly reflects the pathogenesis and pathological characteristics of Parkinson’s disease.
To establish subacute and Chronic Parkinson's disease models using MPTP, and to observe the similarities and differences between the two animal models in behavior, histopathology, and changes in related protein levels, and their differences with the clinical symptoms of the disease.
Forty C57BL/6J mice were randomized into four groups. In subacute model group, mice were injected with MPTP 25 mg/kg/d intraperitoneally for 7 days. In control group 1, injected with normal saline intraperitoneally; chronic model group, injected with MPTP subcutaneously at 25 mg/kg, and then with probenecid at 250 mg/kg intraperitoneally. In the chronic model group, MPTP+probenecid were injected at an interval of 3.5 days for a total of 10 times to induce a chronic model. In control group 2, mice were injected with probenecid intraperitoneally. The behavioral changes of mice were tested by the rotarod and the pole tests, and the distribution of tyrosine hydroxylase positive cells in the substantia nigra was detected by immunofluorescence staining, and the expression level of tyrosine hydroxylase protein in brain tissue was detected by western blot. The study protocol was approved by the Institutional Animal Care and Use Committee (IACUC) of Guangdong Laboratory Animal Monitoring Institute with AAALAC Certification (No. IACUC 2020137).
In the subacute mouse model, the results of the rotarod test showed that the residence time of the mice on the accelerated rotating rod was significantly reduced compared with the control group 1 (P < 0.05). In the pole test, the time for the mice to move from the top of the pole to the bottom increased significantly compared with the control group 1 (P < 0.05). However, the number of tyrosine hydroxylase positive cells in the substantia nigra and the expression of tyrosine hydroxylase protein were not significantly different from those of the control group 1. In the chronic mouse model, there was no significant difference in the total time of rotarod stay and the pole test compared with the control group 2, but the number of tyrosine hydroxylase positive cells in the substantia nigra and the tyrosine hydroxylase protein expression level were significantly lower than those of the control group 2 (P < 0.05). Therefore, MPTP-induced subacute and chronic Parkinson’s model mouse models show partial similar phenotypes to human Parkinson's disease in sports injuries and pathological changes due to differences in modeling methods, suggesting that it is necessary to select an appropriate animal model based on the study purpose.
Parkinson’s disease, MPTP, subacute model, chronic model, tyrosine hydroxylase