A highly reproducible rotenone model of Parkinson's disease.
A highly reproducible rotenone model of Parkinson's disease.
复制标题
DOI：
10.1016/j.nbd.2009.01.016
复制
发表时间：
2009-05
影响因子：
6.1
通讯作者：
Greenamyre JT
中科院分区：
文献类型：
--
作者：
Cannon JR;Tapias V;Na HM;Honick AS;Drolet RE;Greenamyre JT
帕金森病（PD）的全身鱼藤酮模型准确地复制了人类PD病理学的许多方面，并提供了对PD发病机制的见解。鱼藤酮模型的主要局限性是其变异性，无论是在发展一个明确的黑质纹状体病变的动物的百分比和病变的程度。本文的目标是开发一种改进的、高度可重复的PD鱼藤酮模型。在这些研究中，三个年龄组（3、7或12-14个月）的雄性刘易斯大鼠通过每日腹膜内注射给予鱼藤酮（2.75或3.0 mg/kg/天）。所有鱼藤酮治疗的动物出现运动迟缓，姿势不稳定和/或僵硬，阿扑吗啡逆转，与黑质纹状体多巴胺系统的病变一致。当PD表型变得衰弱时，处死动物。鱼藤酮治疗引起了45%的损失酪氨酸羟化酶阳性黑质神经元和纹状体多巴胺的相应损失。此外，在鱼藤酮处理的动物中，在黑质的多巴胺神经元中观察到α-突触核蛋白和聚泛素阳性聚集体。总之，这个版本的鱼藤酮模型是高度可重复的，可以提供一个很好的工具来测试新的神经保护策略。
The systemic rotenone model of Parkinson's disease (PD) accurately replicates many aspects of the pathology of human PD and has provided insights into the pathogenesis of PD. The major limitation of the rotenone model has been its variability, both in terms of the percentage of animals that develop a clear-cut nigrostriatal lesion and the extent of that lesion. The goal here was to develop an improved and highly reproducible rotenone model of PD. In these studies, male Lewis rats in three age groups (3, 7 or 12-14 months) were administered rotenone (2.75 or 3.0 mg/kg/day) in a specialized vehicle by daily intraperitoneal injection. All rotenone-treated animals developed bradykinesia, postural instability, and/or rigidity, which were reversed by apomorphine, consistent with a lesion of the nigrostriatal dopamine system. Animals were sacrificed when the PD phenotype became debilitating. Rotenone treatment caused a 45% loss of tyrosine hydroxylase-positive substantia nigra neurons and a commensurate loss of striatal dopamine. Additionally, in rotenone-treated animals, α-synuclein and poly-ubiquitin positive aggregates were observed in dopamine neurons of the substantia nigra. In summary, this version of the rotenone model is highly reproducible and may provide an excellent tool to test new neuroprotective strategies.
登录
查看更多内容
影响因子：
4.2
作者：
Biehlmaier, Oliver;Alam, Mesbah;Schmidt, Werner J.
通讯作者：
Schmidt, Werner J.
影响因子：
9.9
作者：
Liou, HH;Tsai, MC;Chen, RC
通讯作者：
Chen, RC
影响因子：
2.7
作者：
Alam, M;Schmidt, WJ
通讯作者：
Schmidt, WJ
影响因子：
5.3
作者：
Fleming, SM;Zhu, CN;Chesselet, MF
通讯作者：
Chesselet, MF
影响因子：
2.9
作者：
Cannon, Jason R.;Keep, Richard F.;Xi, Guohua
通讯作者：
Xi, Guohua