帕金森病(Parkinson’sdisease,PD)是一种严重影响人类健康的神经退行性疾病。在PD的实验室研究中,腹腔注射1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的小鼠模型被广泛使用。然而,关于模拟PD症状和病理的模型有效性一直存在争议,MPTP治疗后行为和病理特征的时变发展仍不清楚。为了解决这些问题,我们设计了一系列实验来评估不同时间点的PD模型。我们通过腹腔注射MPTP连续5天构建亚急性PD小鼠模型。转杆试验,在最后一次注射MPTP后的-5、1、5、7、14、21和28天进行开放场测试和酪氨酸羟化酶的免疫组织化学染色。结果显示,在最后一次MPTP给药后5天,典型的运动障碍在旋转杆试验中开始出现,并在整个试验中保持稳定。同时,我们还观察到黑质致密质中酪氨酸羟化酶(TH)阳性细胞的丢失和纹状体中TH含量的降低,但注射21天后黑质致密质中的这种病理变化逆转。此外,通过MPTP,小鼠在野外试验中的自发运动保持不变。这项研究表明MPTP神经毒性的时间依赖性,损害运动功能和组织学特征,并证实了MPTP注射后的症状发生时间。为今后MPTP诱导PD的研究提供参考。
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.