The spatiotemporal changes in dopamine, neuromelanin and iron characterizing Parkinson's disease.
The spatiotemporal changes in dopamine, neuromelanin and iron characterizing Parkinson's disease.
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DOI：
10.1093/brain/awab191
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发表时间：
2021-11-29
期刊：
影响因子：
--
通讯作者：
Lehéricy S
中科院分区：
文献类型：
--
作者：
Biondetti E;Santin MD;Valabrègue R;Mangone G;Gaurav R;Pyatigorskaya N;Hutchison M;Yahia-Cherif L;Villain N;Habert MO;Arnulf I;Leu-Semenescu S;Dodet P;Vila M;Corvol JC;Vidailhet M;Lehéricy S
在帕金森氏病中，纹状体多巴胺能功能进行性降低，含神经黑素的多巴胺能神经元丢失，黑质铁沉积增加。我们测试的假设之间的关系的多巴胺能系统的损害和铁代谢的变化。基于前驱期和早期临床帕金森病患者的成像数据，我们评估了黑质纹状体系统感觉运动、联想和边缘系统区域的时空顺序变化和关系。帕金森病（病程< 4年）或特发性REM睡眠行为障碍（帕金森病的前驱形式）患者和健康对照组进行纵向检查（基线和2年随访）。进行神经黑色素和铁敏感MRI和多巴胺转运蛋白单光子发射断层扫描，以评估黑质纹状体神经黑色素、铁和多巴胺水平。对于黑质纹状体系统的所有三个功能区域，分别在临床上最受影响和最不受影响的半球中，进行了以下工作：纹状体多巴胺和铁，黑质神经黑色素和铁的横截面和纵向组间差异分析;在帕金森病患者中，指数拟合分析评估前驱期的持续时间和多巴胺变化的时间顺序，神经黑色素或铁相对于对照的变化;以及逐体素相关分析以研究黑质延髓部中多巴胺-铁、多巴胺-神经黑色素和神经黑色素-铁的伴随空间变化。多巴胺能变化的时间顺序如下已知的空间模式的进展，首先涉及感觉运动，然后关联和边缘纹状体和黑质区域。首先发生纹状体多巴胺能去神经支配，其次是铁代谢异常，最后是黑质神经黑色素的变化，这与在纹状体中观察到的空间和时间梯度相同，但在时间上发生了变化。总之，多巴胺能纹状体功能障碍和细胞损失在黑质pars延髓与黑质铁含量增加。Biondetti等人在前驱期和早期临床帕金森病患者中使用多模式成像（MRI和SPECT），揭示了多巴胺能变化、异常铁代谢和神经黑色素变化，首先是感觉运动区，然后是黑质纹状体系统的联合区，最后是边缘区。
In Parkinson’s disease, there is a progressive reduction in striatal dopaminergic function, and loss of neuromelanin-containing dopaminergic neurons and increased iron deposition in the substantia nigra. We tested the hypothesis of a relationship between impairment of the dopaminergic system and changes in the iron metabolism. Based on imaging data of patients with prodromal and early clinical Parkinson’s disease, we assessed the spatiotemporal ordering of such changes and relationships in the sensorimotor, associative and limbic territories of the nigrostriatal system. Patients with Parkinson’s disease (disease duration < 4 years) or idiopathic REM sleep behaviour disorder (a prodromal form of Parkinson’s disease) and healthy controls underwent longitudinal examination (baseline and 2-year follow-up). Neuromelanin and iron sensitive MRI and dopamine transporter single-photon emission tomography were performed to assess nigrostriatal levels of neuromelanin, iron, and dopamine. For all three functional territories of the nigrostriatal system, in the clinically most and least affected hemispheres separately, the following was performed: cross-sectional and longitudinal intergroup difference analysis of striatal dopamine and iron, and nigral neuromelanin and iron; in Parkinson’s disease patients, exponential fitting analysis to assess the duration of the prodromal phase and the temporal ordering of changes in dopamine, neuromelanin or iron relative to controls; and voxel-wise correlation analysis to investigate concomitant spatial changes in dopamine-iron, dopamine-neuromelanin and neuromelanin-iron in the substantia nigra pars compacta. The temporal ordering of dopaminergic changes followed the known spatial pattern of progression involving first the sensorimotor, then the associative and limbic striatal and nigral regions. Striatal dopaminergic denervation occurred first followed by abnormal iron metabolism and finally neuromelanin changes in the substantia nigra pars compacta, which followed the same spatial and temporal gradient observed in the striatum but shifted in time. In conclusion, dopaminergic striatal dysfunction and cell loss in the substantia nigra pars compacta are interrelated with increased nigral iron content. Using multi-modal imaging (MRI and SPECT) in patients with prodromal and early clinical Parkinson’s disease, Biondetti et al. reveal dopaminergic changes, abnormal iron metabolism and neuromelanin changes first in the sensorimotor, then the associative and finally the limbic regions of the nigrostriatal system.
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DOI：
10.1002/mds.26417
发表时间：
2016-03
期刊：
Movement disorders : official journal of the Movement Disorder Society
影响因子：
--
作者：
Du G;Liu T;Lewis MM;Kong L;Wang Y;Connor J;Mailman RB;Huang X
通讯作者：
Huang X
影响因子：
11
作者：
HUGHES, AJ;DANIEL, SE;LEES, AJ
通讯作者：
LEES, AJ
影响因子：
14.5
作者：
Biondetti, Emma;Gaurav, Rahul;Lehericy, Stephane
通讯作者：
Lehericy, Stephane
影响因子：
4.6
作者：
Dusek, Petr;Ibarburu, Veronika Lorenzo y Losada;Sonka, Karel
通讯作者：
Sonka, Karel
影响因子：
16.6
作者：
Carballo-Carbajal, Iria;Laguna, Ariadna;Vila, Miquel
通讯作者：
Vila, Miquel