Long-term Changes in the Nigrostriatal Pathway in the MPTP Mouse Model of Parkinson's Disease
Long-term Changes in the Nigrostriatal Pathway in the MPTP Mouse Model of Parkinson's Disease
复制标题
帕金森病 MPTP 小鼠模型中黑质纹状体通路的长期变化
DOI：
10.1016/j.neuroscience.2017.11.041
复制
发表时间：
2018-01-15
期刊：
影响因子：
3.3
通讯作者：
Huang, Fang
中科院分区：
文献类型：
--
作者：
Huang, Dongping;Wang, Zishan;Huang, Fang
帕金森病是一种常见的进行性神经退行性疾病。1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）小鼠PD模型被广泛用于研究这种疾病的进展。行为障碍与基底神经节多巴胺能系统的损伤密切相关。在这里，MPTP诱导的小鼠行为和神经胶质细胞活化的变化在治疗后的不同时间点进行了评估，并在黑质纹状体通路的长期变化进行了分析。我们发现暴露于MPTP的小鼠在注射后65天在转棒测试和杆测试中显示完全恢复，但在钢丝悬挂测试中没有。在MPTP处理的小鼠的黑质纹状体通路中揭示了小胶质细胞的双相激活。然而，星形胶质细胞的激活分别在纹状体和黑质中显示出近似钟形动力学和近似S形动力学。此外，补体成分3（C3）阳性神经毒性星形胶质细胞在MPTP治疗小鼠黑质的数量随着时间的推移而增加，并在42天达到最大值，并在74天下降，治疗后。3个月后，MPTP损伤的多巴胺能系统部分恢复。病理生理事件的时间进程对PD的干预或治疗具有重要意义。(C)2017年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Parkinson's disease (PD) is a common and progressive neurodegenerative disorder. The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD is widely used to study the progression of this disease. Behavior impairment is closely related to the damage of the dopaminergic system in the basal ganglia. Here, MPTP-induced changes in mouse behavior and glial activation were evaluated at different time points after the treatment and the long-term changes in the nigrostriatal pathway were analyzed. We found that mice exposed to MPTP displayed a full recovery in the rotarod test and the pole test but not in the wire hanging test at 65 days post-injection. A biphasic activation of microglial cells was revealed in the nigrostriatal pathway of MPTP-treated mice. However, activation of astrocytes displayed an approximately bell-shaped kinetics and an approximately S-shaped kinetics in the striatum and the substantia nigra, respectively. In addition, the numbers of complement component 3 (C3)-positive neurotoxic astrocytes in the substantia nigra of MPTP-treated mice increased with time and reached a maximum at 42 days, and declined at 74 days, after the treatment. Three months later, the dopaminergic system was partially recovered from the lesion of MPTP. The time course of pathophysiological events has important implications for the interventions or treatment of PD. (C) 2017 IBRO. Published by Elsevier Ltd. All rights reserved.