School of Pharmacy, Faculty of Health Sciences, P. O. Box 1627, University of Eastern Finland, Kuopio Campus, Kuopio 70211, Finland.
Brain Res. 2011 Mar 25;1382:37-44. doi: 10.1016/j.brainres.2011.01.064. Epub 2011 Jan 26.
The presynaptic protein alpha-synuclein (α-syn) plays a role in dopaminergic neurotransmission in the nigrostriatal dopaminergic system. Mutations in this protein have been linked to pathogenesis of Parkinson's disease. However, the details of regulation of dopamine homeostasis by α-syn and its molecular targets are generally unknown. We investigated the effect of α-syn deletion on striatal dopaminergic homeostasis. Two α-syn deficient mouse lines, one carrying a spontaneous deletion of α-syn locus and the other a transgenic α-syn knockout, were used in the study. Stimulated and basal extracellular dopamine levels were determined in the dorsal striatum by in vivo voltammetry and in vivo microdialysis, respectively. Dopamine transporter expression was studied by immunohistochemistry. Stimulated dopamine overflow and basal extracellular dopamine levels were higher in mice lacking α-syn with a concomitant decrease in dopamine transporter expression and reuptake in the dorsal striatum. We show that α-syn deletion produces significant adaptive changes in the striatal dopaminergic system via modulation of reuptake.
突触前蛋白α-突触核蛋白（α-syn）在黑质纹状体多巴胺能系统的多巴胺能神经传递中发挥作用。该蛋白的突变与帕金森病的发病机制有关。然而，α-syn 调节多巴胺动态平衡的详细机制及其分子靶点通常尚不清楚。我们研究了α-syn 缺失对纹状体多巴胺能动态平衡的影响。研究中使用了两种α-syn 缺失的小鼠品系，一种携带α-syn 基因座的自发缺失，另一种携带转基因α-syn 敲除。通过在体伏安法和在体微透析分别测定背侧纹状体中刺激和基础细胞外多巴胺水平。通过免疫组织化学研究多巴胺转运体的表达。缺乏 α-syn 的小鼠刺激的多巴胺溢出和基础细胞外多巴胺水平更高，同时背侧纹状体中的多巴胺转运体表达和再摄取减少。我们表明，α-syn 的缺失通过调节再摄取，对纹状体多巴胺能系统产生显著的适应性变化。
