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大鼠单侧纹状体损伤和内侧前脑束损伤后早期纹状体 D2 样受体功能的不同。

Different striatal D2-like receptor function in an early stage after unilateral striatal lesion and medial forebrain bundle lesion in rats.

机构信息

Department of Neurosurgery, Hamamatsu University School of Medicine 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan.

出版信息

Brain Res. 2010 Mar 4;1317:227-35. doi: 10.1016/j.brainres.2009.12.048. Epub 2010 Jan 4.

Abstract

Unilateral striatal lesion and complete medial forebrain bundle (MFB) lesion by 6-hydroxydopamine in rats have been widely used as Parkinson disease (PD) models. However, the difference of pre- and post-synaptic dopamine (DA) system in these two models are not well concerned. In order to investigate the pathophysiologic difference between the MFB lesion rats and striatal lesion rats, we studied the variation of pre-synaptic DA transporter and post-synaptic D(2)-like receptor in nigrostriatal DA system using binding assay, behavioral test and a small animal PET. Our data showed that there was a same tendency of the striatal DA transporter decrease both in MFB lesion rats and striatal lesion rats 4 weeks after lesion, however, it showed increase (up-regulation) of D(2)-like receptor in the MFB lesion rats, whereas showed decrease (down-regulation) in the striatal lesion rat. This finding strongly indicated the different dynamic pathophysiologic process between the MFB lesion model and striatal lesion model. MFB lesion model mimics an early stage of PD, whereas striatal lesion model mimics Parkinson syndrome, such as vascular Parkinson syndrome. Such difference should be taken into account in the selection of these model systems.

摘要

单侧纹状体损伤和内侧前脑束(MFB)损伤通过 6-羟多巴胺在大鼠中被广泛用作帕金森病(PD)模型。然而,这两种模型中突触前和突触后多巴胺(DA)系统的差异并没有得到很好的关注。为了研究 MFB 损伤大鼠和纹状体损伤大鼠之间的病理生理差异,我们使用结合测定、行为测试和小动物 PET 研究了黑质纹状体 DA 系统中突触前 DA 转运体和突触后 D2 样受体的变化。我们的数据表明,在损伤后 4 周,MFB 损伤大鼠和纹状体损伤大鼠的纹状体 DA 转运体均呈下降趋势,但 MFB 损伤大鼠的 D2 样受体呈上升(上调)趋势,而纹状体损伤大鼠的 D2 样受体则呈下降(下调)趋势。这一发现强烈表明 MFB 损伤模型和纹状体损伤模型之间存在不同的动态病理生理过程。MFB 损伤模型模拟 PD 的早期阶段,而纹状体损伤模型模拟帕金森综合征,如血管性帕金森综合征。在选择这些模型系统时,应考虑到这种差异。

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