1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)小鼠模型是最常见的帕金森病(PD)动物模型之一。它分为三种类型:急性,亚急性,和慢性中毒模型。亚急性模型因其周期短且与PD相似而备受关注。然而,小鼠亚急性MPTP中毒是否模拟PD的运动和认知障碍仍存在很大争议。因此,本研究使用开放场重新评估小鼠亚急性MPTP中毒的行为表现,旋转杆,Y迷宫,建模后不同时间点(1、7、14和21天)的步态分析。目前的研究结果表明,尽管使用亚急性方案的MPTP治疗的小鼠表现出严重的多巴胺能神经元丢失和明显的星形胶质细胞增生,他们没有表现出显著的运动和认知缺陷。此外,混合谱系激酶结构域样(MLKL)的表达,坏死的标志,MPTP中毒小鼠的腹侧中脑和纹状体也显着增加。这显然意味着坏死可能在MPTP诱导的神经变性中起重要作用。总之,本研究的结果表明,亚急性MPTP中毒小鼠可能不是研究帕金森病的合适模型。然而,它可以帮助揭示PD的早期病理生理学,并研究早期PD中发生的代偿机制,以防止行为缺陷的出现。
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mice model is one of the most common animal models for Parkinson\'s disease (PD). It is classified into three types: acute, subacute, and chronic intoxication models. The subacute model has attracted much attention for its short period and similarity to PD. However, whether subacute MPTP intoxication in mouse mimics the movement and cognitive disorders of PD still remains highly controversial. Therefore, the present study reassessed the behavioral performances of subacute MPTP intoxication in mice using open field, rotarod, Y maze, and gait analysis at different time points (1, 7, 14, and 21 days) after modeling. Results of the current study showed that although MPTP-treated mice using subacute regimen showed severe dopaminergic neuronal loss and evident astrogliosis, they failed to display significant motor and cognitive deficits. Besides, expression of mixed lineage kinase domain-like (MLKL), a marker of necroptosis, was also significantly increased in the ventral midbrain and striatum of MPTP-intoxicated mice. This evidently implies that necroptosis may play an important role in MPTP-induced neurodegeneration. In conclusion, the findings of the present study suggest that subacute MPTP-intoxicated mice may not be a suitable model for studying parkinsonism. However, it can help in revealing the early pathophysiology of PD and studying the compensatory mechanisms which occur in early PD that prevent the emergence of behavioral deficits.