Stefanova N, Lundblad M, Tison F, Poewe W, Cenci M A, Wenning G K
Department of Neurology, University Hospital of Innsbruck, Innsbruck, Austria.
Neurobiol Dis. 2004 Apr;15(3):630-9. doi: 10.1016/j.nbd.2003.11.025.
We examined the role of a striatal lesion in the development of L-DOPA-induced abnormal involuntary movements (AIMs) using the double lesion rat model of striatonigral degeneration (SND), the underlying neuropathological substrate of parkinsonism associated with multiple system atrophy (MSA-P), in comparison to a Parkinson's disease (PD) rat model. L-DOPA administration reliably induced AIMs in SND and PD rats in a dose-dependent fashion. AIMs occurred significantly earlier in SND compared to PD rats. There was a mild, but significant, transient increase of orolingual AIMs during the first week of low-dose L-DOPA treatment in SND. Whereas L-DOPA significantly improved contralateral forelimb akinesia in PD rats, there was no beneficial effect in SND rats. Striatal FosB/Delta FosB up-regulation in SND and PD rats correlated with the severity of L-DOPA-induced dyskinesias. Pulsatile L-DOPA administration in the double lesion SND rat model replicates salient features of the human disease MSA-P, including loss of the anti-akinetic L-DOPA response and induction of dyskinesias with transient orolingual predominance.
我们使用纹状体黑质变性（SND）的双损伤大鼠模型（帕金森病相关多系统萎缩（MSA-P）的潜在神经病理学基础），与帕金森病（PD）大鼠模型相比，研究了纹状体损伤在左旋多巴诱导的异常不自主运动（AIMs）发展中的作用。给予左旋多巴能以剂量依赖的方式在SND和PD大鼠中可靠地诱导出AIMs。与PD大鼠相比，AIMs在SND大鼠中出现得明显更早。在SND大鼠中，低剂量左旋多巴治疗的第一周，口面部AIMs有轻微但显著的短暂增加。虽然左旋多巴能显著改善PD大鼠对侧前肢运动不能，但对SND大鼠没有有益作用。SND和PD大鼠纹状体中FosB/ΔFosB上调与左旋多巴诱导的运动障碍严重程度相关。在双损伤SND大鼠模型中脉冲式给予左旋多巴可重现人类疾病MSA-P的显著特征，包括失去抗运动不能的左旋多巴反应以及诱导以口面部短暂占优势的运动障碍。
