Qi Yue, Zhang Ziwei, Xue Jinhua, Yao Suhua, Lu Xiaying, Tang Xiaolu
Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of Education, Jiangxi Province Key Laboratory of Pharmacology of Traditional Chinese Medicine, Ganzhou Key Laboratory of Neuroinflammation Research, School of Basic Medicine Sciences, Gannan Medical University, Ganzhou, China.
Department of Basic Medicine, School of Public Health and Health, Xinyu University, Xinyu, China.
FASEB J. 2025 Jul 15;39(13):e70822. doi: 10.1096/fj.202500467RR.
Parkinson's disease (PD), a prevalent neurodegenerative disorder, is characterized by the selective and progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta, the presence of Lewy bodies (LBs) within neurons, and gliosis. The mouse model induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is one of the most commonly utilized animal models for PD; however, its ability to accurately replicate the full spectrum of motor and non-motor symptoms remains contentious. In this study, we employed novel MPTP administration regimens (160 and 240 mg/kg) to examine the behavioral phenotype and pathological alterations induced by MPTP injury, utilizing a combination of behavioral, molecular, and morphological methodologies. Our findings indicate that MPTP-induced subacute PD mice exhibited a significant loss of dopaminergic neurons in the ventral midbrain, accompanied by diffuse astrogliosis and activated microglia. Nonetheless, these mice did not display other prominent movement disorders or mood abnormalities, aside from the gait disturbances associated with the administered MPTP dose. Consequently, we propose that the MPTP-induced subacute PD mouse model utilized in this study represents an early preclinical stage analogous to that observed in human PD patients.
帕金森病（PD）是一种常见的神经退行性疾病，其特征是黑质致密部多巴胺能神经元的选择性和进行性退化、神经元内路易小体（LBs）的存在以及胶质细胞增生。由神经毒素1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的小鼠模型是最常用于PD研究的动物模型之一；然而，其准确复制所有运动和非运动症状的能力仍存在争议。在本研究中，我们采用了新的MPTP给药方案（160和240mg/kg），结合行为学、分子学和形态学方法，研究MPTP损伤诱导的行为表型和病理改变。我们的研究结果表明，MPTP诱导的亚急性PD小鼠腹侧中脑多巴胺能神经元显著丢失，伴有弥漫性星形胶质细胞增生和小胶质细胞活化。尽管如此，除了与所给MPTP剂量相关的步态障碍外，这些小鼠并未表现出其他明显的运动障碍或情绪异常。因此，我们认为本研究中使用的MPTP诱导的亚急性PD小鼠模型代表了类似于人类PD患者所观察到的早期临床前阶段。
