Ding Yunmin, Restrepo Jacqueline, Won Lisa, Hwang Dong-Youn, Kim Kwang-Soo, Kang Un Jung
Department of Neurology, University of Chicago, Chicago, IL 60637, USA.
Neurobiol Dis. 2007 Jul;27(1):11-23. doi: 10.1016/j.nbd.2007.03.013. Epub 2007 Apr 10.
L-DOPA-induced dyskinesia (LID) is one of the main limitations of long term L-DOPA use in Parkinson's disease (PD) patients. We show that chronic L-DOPA treatment induces novel dyskinetic behaviors in aphakia mouse with selective nigrostriatal deficit mimicking PD. The stereotypical abnormal involuntary movements were induced by dopamine receptor agonists and attenuated by antidyskinetic agents. The development of LID was accompanied by preprodynorphin and preproenkephalin expression changes in the denervated dorsal striatum. Increased FosB-expression was also noted in the dorsal striatum. In addition, FosB expression was noted in the pedunculopontine nucleus and the zona incerta, structures previously not examined in the setting of LID. The aphakia mouse is a novel genetic model with behavioral and biochemical characteristics consistent with those of PD dyskinesia and provides a more consistent, convenient, and physiologic model than toxic lesion models to study the mechanism of LID and to test therapeutic approaches for LID.
左旋多巴诱发的异动症（LID）是帕金森病（PD）患者长期使用左旋多巴的主要限制之一。我们发现，慢性左旋多巴治疗会在无晶状体小鼠中诱发新的异动行为，该小鼠具有模拟PD的选择性黑质纹状体缺陷。刻板的异常不自主运动由多巴胺受体激动剂诱发，并被抗异动剂减弱。LID的发展伴随着去神经支配的背侧纹状体中前强啡肽原和前脑啡肽原表达的变化。在背侧纹状体中也观察到FosB表达增加。此外，在脚桥核和未定带中也观察到FosB表达，这些结构以前在LID研究中未被检测。无晶状体小鼠是一种新型遗传模型，其行为和生化特征与PD异动症一致，与毒性损伤模型相比，它为研究LID机制和测试LID治疗方法提供了更一致、方便和生理学的模型。
