Ren Jinfeng, Liu Tongzheng, You Luyan, Hu Minghui, Zhu Jianping, Wang Xinyu, Zhang Hao, Zhang Jiayu, Li Zifa, Wei Sheng, Geng Xiwen
Key Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Jinan, 250355, PR China.
Shandong Provincial Engineering Research Center for the Prevention and Treatment of Major Brain Diseases with Traditional Chinese Medicine (PTMBD), Shandong University of Traditional Chinese Medicine, Jinan, 250355, PR China.
Heliyon. 2024 Jul 4;10(13):e34082. doi: 10.1016/j.heliyon.2024.e34082. eCollection 2024 Jul 15.
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.
帕金森病(PD)是一种严重的神经退行性疾病,会扰乱人类健康。在关于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,关于该模型模拟PD症状和病理的有效性存在争议,且MPTP处理后行为和病理特征的随时间变化发展仍不清楚。为了解决这些问题,我们设计了一系列实验,在不同时间点评估这个PD模型。我们通过连续5天腹腔注射MPTP构建了亚急性PD小鼠模型。在最后一次注射MPTP后的-5、1、5、7、14、21和28天进行转棒试验、旷场试验以及酪氨酸羟化酶的免疫组织化学染色。结果显示,在最后一次给予MPTP后5天,转棒试验中出现典型的运动障碍,伴有明显的平衡功能损害,且在整个实验过程中保持稳定。同时,我们还观察到黑质致密部酪氨酸羟化酶(TH)阳性细胞的丢失以及纹状体中TH含量的降低,但黑质致密部的这种病理变化在注射后21天逆转。此外,MPTP对旷场试验中小鼠的自发运动没有影响。本研究表明MPTP神经毒性损害运动功能和组织学特征具有时间依赖性,并确定了MPTP注射后症状出现的时间,为未来关于MPTP诱导的PD的研究提供了参考。