Striatal fosB expression is causally linked with L-DOPA-induced abnormal involuntary movements and the associated upregulation of striatal prodynorphin mRNA in a rat model of Parkinson's disease
Striatal fosB expression is causally linked with L-DOPA-induced abnormal involuntary movements and the associated upregulation of striatal prodynorphin mRNA in a rat model of Parkinson's disease
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DOI：
10.1006/nbdi.1999.0259
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发表时间：
1999-12-01
影响因子：
6.1
通讯作者：
Cenci, MA
中科院分区：
文献类型：
--
作者：
Andersson, M;Hilbertson, A;Cenci, MA
患有单侧多巴胺去神经损伤的大鼠持续3周，每日左旋多巴剂量在帕金森病的治疗范围内。在大多数接受左旋多巴治疗的动物中，慢性左旋多巴逐渐引起异常的不自主运动，影响病变对侧身体一侧的颅、躯干和肢体肌肉。这种效应与诱导纹状体亚区中与左旋多巴引起的运动类型相关的fosb样免疫反应蛋白相一致。诱导蛋白与prodynorphin mRNA存在区域共定位和细胞共定位。纹状体内注入fosB反义抑制纹状体亚区相关的运动障碍的发生，并产生局部特异性下调prodynorphin mRNA。这些数据提供了令人信服的证据，证明纹状体fosB诱导大鼠左旋多巴诱导的运动障碍的发展，以及fosB相关转录因子对促运动啡基因表达的积极调节。(C) 1999学术出版社。
Rats with unilateral dopamine-denervating lesions sustained a 3-week treatment with a daily L-DOPA dose that is in the therapeutic range for Parkinson's disease. In most of the treated animals, chronic L-DOPA administration gradually induced abnormal involuntary movements affecting cranial, trunk, and limb muscles on the side of the body contralateral to the lesion. This effect was paralleled by an induction of FosB-like immunoreactive proteins in striatal subregions somatotopically related to the types of movements that had been elicited by L-DOPA. The induced proteins showed both regional and cellular colocalization with prodynorphin mRNA. Intrastriatal infusion of fosB antisense inhibited the development of dyskinetic movements that were related to the striatal subregion targeted and produced a local specific downregulation of prodynorphin mRNA. These data provide compelling evidence of a causal role for striatal fosB induction in the development of L-DOPA-induced dyskinesia in the rat and of a positive regulation of prodynorphin gene expression by FosB-related transcription factors. (C) 1999 Academic Press.