Performance of movement in hemiparkinsonian rats influences the modifications induced by dopamine agonists in striatal efferent dynorphinergic neurons
Performance of movement in hemiparkinsonian rats influences the modifications induced by dopamine agonists in striatal efferent dynorphinergic neurons
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DOI：
10.1016/j.expneurol.2013.03.002
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发表时间：
2013-09-01
影响因子：
5.3
通讯作者：
Simola, Nicola
中科院分区：
文献类型：
--
作者：
Frau, Lucia;Morelli, Micaela;Simola, Nicola
本课题组以前的一项研究表明，多巴胺激动剂药物诱导的偏侧帕金森病大鼠单侧6-羟基多巴胺(6-OHDA)损伤后的运动表现，控制着对随后的多巴胺能刺激(启动模型)的敏化运动反应的发生。在本研究中，我们考察了运动行为(旋转行为)对纹状体启动所诱发的分子事件的影响。为此，单侧6-羟色胺损毁大鼠在固定或自由活动状态下注射阿朴吗啡(0.2mgkg)(启动诱导)，3d后给予D-1受体激动剂SKF 38393(启动表达)。对纹状体间接和直接纹状体通路的标志物脑啡肽和强啡肽以及GAD67基因表达的评估表明，无论是固定还是自由活动，经SKF 38393处理的大鼠纹状体中强啡肽的表达均增加，而脑啡肽和GAD67的表达没有任何变化。相反，纹状体早期基因ZIF-268mRNA的评估显示，在给药SKF 38393后，无论是预激还是非预激的大鼠，纹状体中ZIF-268mRNA的表达都普遍增加。然而，在单细胞水平上对ZIF-268mRNA的检测显示，只有未被束缚的强啡肽(+)神经元在SKF 38393的刺激下显示出明显更多的ZIF-268阳性银粒。ZIF-268在强啡肽能纹状体黑质传出神经元中的这种选择性激活表明，在多巴胺去神经支配的条件下，对多巴胺能药物的反应的运动表现是选定的纹状体传出神经元出现神经化学修饰的关键。此外，这些结果可能提供关于在导致帕金森氏病运动障碍的复杂过程中发生的第一个初始分子事件的信息。(C)2013 Elsevier Inc.保留所有权利。
A previous study of our group demonstrated that movement performance induced by dopamine agonist drugs in hemiparkinsonian rats unilaterally lesioned with 6-hydroxydopamine (6-OHDA), governs the occurrence of a sensitized motor response to a subsequent dopaminergic challenge (priming model). In the present study, we examined the influence of movement performance (rotational behavior) on the molecular events induced by priming in the striatum. To this end, unilaterally 6-OHDA-lesioned rats were primed with apomorphine (0.2 mg/kg) in immobilized or freely moving conditions (priming induction) and 3 days later the D-1 receptor agonist SKF 38393 was administered (priming expression). Evaluation of striatal mRNA for enkephalin and dynorphin, markers of the indirect and direct striatonigral pathways, and of GAD67 showed an increase in dynorphin in primed SKF 38393-treated rats, no matter whether immobilized or freely moving during priming induction, whilst enkephalin and GAD67 did not show any changes. In contrast, evaluation of mRNA for the early gene zif-268 in the striatum showed a generalized increase after administration of SKF 38393, in both primed and unprimed rats. However, examination of zif-268 mRNA at the single-cell level, showed that only dynorphin(+) neurons of primed not immobilized rats displayed a significantly higher number of zif-268-positive silver grains in response to the SKF 38393 challenge. This selective activation of zif-268 in dynorphinergic striatonigral efferent neurons demonstrates that movement performance in response to dopaminergic drug administration under conditions of dopamine denervation is critical for the emergence of neurochemical modifications in selected striatal efferent neurons. Furthermore, these results may provide information on the first initial molecular events taking place in the complex processes that lead to dyskinetic movements in Parkinson's disease. (C) 2013 Elsevier Inc. All rights reserved.