Lin Ling, Ye Jing, Zhang Han, Han Zhong-Fu, Zheng Zhi-Hong
Fujian Provincial Key Laboratory of Neuroglia and Disease, Fujian Medical University; Department of Biochemistry and Molecular Biology, Fujian Medical University, Fuzhou, Fujian Province, China.
Department of Biochemistry and Molecular Biology, Fujian Medical University, Fuzhou, Fujian Province, China.
Neural Regen Res. 2018 Jul;13(7):1281-1287. doi: 10.4103/1673-5374.235077.
To prevent and treat Parkinson's disease in its early stages, it is essential to be able to detect the degree of early dopaminergic neuron degeneration. Dopamine transporters (DAT) in the striatum regulate synaptic dopamine levels, and striatal Tc-TRODAT-1 single-photon emission computed tomography (-SPECT) imaging is a marker for presynaptic neuronal degeneration. However, the association between the degree of dopaminergic degeneration and in vivo Tc-TRODAT-1 SPECT imaging is unknown. Therefore, this study investigated the association between the degree of 6-hydroxydopamine (6-OHDA)-induced dopaminergic degeneration and DAT imaging using Tc-TRODAT-1 SPECT in rats. Different degrees of nigrostriatal dopamine depletion were generated by injecting different doses of 6-OHDA (2, 4, and 8 μg) into the right medial forebrain bundle. The degree of nigrostriatal dopaminergic neuron degeneration was assessed by rotational behavior and immunohistochemical staining. The results showed that striatal Tc-TRODAT-1 binding was significantly diminished both in the ipsilateral and the contralateral sides in the 4 and 8 μg 6-OHDA groups, and that DAT Tc-TRODAT-1 binding in the ipsilateral striatum showed a high correlation to apomorphine-induced rotations at 8 weeks post-lesion (r = -0.887, P < 0.01). There were significant correlations between DAT Tc-TRODAT-1 binding in the ipsilateral striatum and the amount of tyrosine hydroxylase immunoreactive neurons in the ipsilateral substantia nigra in the 2, 4, and 8 μg 6-OHDA groups at 8 weeks post-lesion (r = 0.899, P < 0.01). These findings indicate that striatal DAT imaging using Tc-TRODAT-1 is a useful technique for evaluating the severity of dopaminergic degeneration.
为了在帕金森病早期进行预防和治疗，能够检测早期多巴胺能神经元变性的程度至关重要。纹状体中的多巴胺转运体（DAT）调节突触多巴胺水平，而纹状体Tc-TRODAT-1单光子发射计算机断层扫描（-SPECT）成像则是突触前神经元变性的一个标志物。然而，多巴胺能变性程度与体内Tc-TRODAT-1 SPECT成像之间的关联尚不清楚。因此，本研究使用Tc-TRODAT-1 SPECT在大鼠中研究了6-羟基多巴胺（6-OHDA）诱导的多巴胺能变性程度与DAT成像之间的关联。通过向右侧内侧前脑束注射不同剂量的6-OHDA（2、4和8μg）产生不同程度的黑质纹状体多巴胺耗竭。通过旋转行为和免疫组织化学染色评估黑质纹状体多巴胺能神经元变性的程度。结果显示，在4μg和8μg 6-OHDA组中，同侧和对侧纹状体的Tc-TRODAT-1结合均显著减少，并且在损伤后8周，同侧纹状体中的DAT Tc-TRODAT-1结合与阿扑吗啡诱导的旋转高度相关（r = -0.887，P < 0.01）。在损伤后8周，2μg、4μg和8μg 6-OHDA组同侧纹状体中的DAT Tc-TRODAT-1结合与同侧黑质中酪氨酸羟化酶免疫反应性神经元的数量之间存在显著相关性（r = 0.899，P < 0.01）。这些发现表明，使用Tc-TRODAT-1进行纹状体DAT成像对于评估多巴胺能变性的严重程度是一种有用的技术。
