中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (7): 1281-1287.doi: 10.4103/1673-5374.235077

• 原著:退行性病与再生 • 上一篇    下一篇

单光子发射计算机断层成像技术可判定多巴胺能神经元退行性变的严重程度？

  

  • 收稿日期:2018-05-20 出版日期:2018-07-15 发布日期:2018-07-15
  • 基金资助:

    国家自然科学基金（81571250）

Degree of dopaminergic degeneration measured by 99mTc-TRODAT-1 SPECT/CT imaging

Ling Lin1, 2, Jing Ye2, Han Zhang2, Zhong-Fu Han2, Zhi-Hong Zheng1, 2   

  1. 1 Fujian Provincial Key Laboratory of Neuroglia and Disease, Fujian Medical University, Fuzhou, Fujian Province, China;
    2 Department of Biochemistry and Molecular Biology, Fujian Medical University, Fuzhou, Fujian Province, China
  • Received:2018-05-20 Online:2018-07-15 Published:2018-07-15
  • Contact: Zhi-Hong Zheng, M.D.,zhzheng@mail.fjmu.edu.cn
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 81571250

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摘要：

如何早期检测多巴胺能神经元变性程度对于预防和治疗帕金森病至关重要。多巴胺转运体(DAT)的密度可反映纹状体的多巴胺水平。单光子发射计算机断层成像技术(99mTc-TRODAT-1 DAT-SPECT)可用于检测纹状体突触前神经元的退变，但是该检测方法与多巴胺能神经元变性程度之间的关系尚不确定。鉴于此，实验设计利用单光子发射计算机断层扫描检测大鼠纹状体DAT的变化，探讨6-羟基多巴胺诱导的多巴胺神经元毁损程度与DAT变化之间的相关性，将大鼠右侧前脑内侧束注射不同浓度(2，4，8 μg)6-羟基多巴胺产生不同程度的多巴胺能神经元变性。通过旋转行为检测及免疫组织化学染色评估黑质纹状体通路多巴胺神经元毁损程度发现，损伤后8周，6-羟基多巴胺(4，8μg)所致健侧及受损侧纹状体99mTc-TRODAT-1标记的DAT放射活性显著降低，阿扑吗啡诱导的旋转行为显著增加，两者呈负相关(r =-0.887, P ；6-羟基多巴胺(2，4，8 μg)所致的受损侧纹状体99mTc-TRODAT-1标记的DAT放射活性显著降低，同侧黑质酪氨酸羟化酶免疫反应阳性神经元数量显著降低，两者呈正相关(r =0.899, P 。上述结果可证实，99mTc-TRODAT-1标记的纹状体多巴胺转运体成像技术有助于评估多巴胺神经元退行性变的严重程度。 < 0.01)< 0.01)

orcid:0000-0002-6638-6896(Zhi-Hong Zheng)

 

关键词: 帕金森病, 6-羟基多巴胺, 多巴胺能神经元变性, 多巴胺转运体, 99mTc-TRODAT-1, 酪氨酸羟化酶, 黑质, 纹状体, 单光子发射计算机断层扫描, 阿朴吗啡, 神经退行性变, 神经再生

Abstract:

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 99mTc-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 99mTc-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 99mTc-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 99mTc-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 99mTc-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 99mTc-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 99mTc-TRODAT-1 is a useful technique for evaluating the severity of dopaminergic degeneration.

Key words: nerve regeneration, Parkinson’s disease, 6-hydroxydopamine, dopaminergic degeneration, dopamine transporter, 99mTc-TRODAT-1, tyrosine hydroxylase, substantia nigra, striatum, single-photon emission computed tomography, apomorphine, neurodegeneration, neural regeneration