Time association study on a sub-acute mouse model of Parkinson's disease

Abstract

Parkinson's disease (PD) is a severe neurodegenerative disease that disturbs human health. In the laboratory researches about PD, the mice model induced by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was widely used. However, there has been controversy about the model effectiveness to simulate PD symptoms and pathology, and the time-varying development of behavioral and pathological characteristic after MPTP treatment remains unclear. In order to solve these problems, we designed a series of experiments to evaluate this PD model at different time points. We constructed the subacute PD mouse model by intraperitoneal injection of MPTP for 5 consecutive days. The rotarod test, open field test and the immunohistochemical staining of tyrosine hydroxylase were conducted at -5, 1, 5, 7, 14, 21 and 28 days after the last injection of MPTP. The results showed that 5 days after the last MPTP administration, typical motor disorders with significant balance function damage in rotarod test began to appear and remained stable throughout the entire experiment. Simultaneously, we also observed the loss of tyrosine hydroxylase (TH) positive cells in the substantia nigra compacta and reduction of TH content in the striatum but this pathological change in the substantia nigra compacta reversed 21 days after injection. Besides, the spontaneous movement of mice in open field test remained unchanged by MPTP. This research indicated the time-dependence of MPTP neurotoxicity that impair the motor function and histological features and confirmed the symptom occurrence time after MPTP injection, which provides a reference for the future research about MPTP-induced PD.

Keywords: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Mouse model; Open field test; Parkinson's disease; Rotarod; Tyrosine hydroxylase.

Fig. 1

Experimental procedure.

Fig. 2

The time-dependent toxicity of MPTP on the behavior and body weight of mice. A: Schematic diagram of the rotarod; B: Time on rotarod; C: Speed of the rotarod during the fall; D: Schematic diagram of the open field test (OFT); E: Total distance in the OFT; F: Body weight of the mouse. (n = 8 mice/group) *P < 0.05, **P < 0.01 vs. control group (two-tailed unpaired t-test).

Fig. 3

Example of tyrosine hydroxylase immunohistochemical staining with mice brain on different day after MPTP injection. SNc: substantia nigra compacta; STR: striatum.

Fig. 4

Statistical results of immunohistochemical staining. A: Number of tyrosine hydroxylase positive (TH⁺) cells in substantia nigra compacta. B: Light intensity in sections of striatum with TH immunohistochemical staining. (n = 3 mice/group) *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, vs. the day before the intraperitoneal injection of MPTP (−5 day) (one-way ANOVA).