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Striatal and cerebellar vesicular acetylcholine transporter expression is disrupted in human DYT1 dystonia.
在人类DYT1肌张力障碍中,纹状体和小脑泡状乙酰胆碱转运蛋白的表达被破坏。
- 影响因子:0
- DOI:10.1093/brain/awaa465
- 作者列表:"Mazere J","Dilharreguy B","Catheline G","Vidailhet M","Deffains M","Vimont D","Ribot B","Barse E","Cif L","Mazoyer B","Langbour N","Pisani A","Allard M","Lamare F","Guehl D","Fernandez P","Burbaud P
- 发表时间:2021-04-12
Abstract
:Early-onset torsion dystonia (TOR1A/DYT1) is a devastating hereditary motor disorder whose pathophysiology remains unclear. Studies in transgenic mice suggested abnormal cholinergic transmission in the putamen, but this has not yet been demonstrated in humans. The role of the cerebellum in the pathophysiology of the disease has also been highlighted but the involvement of the intrinsic cerebellar cholinergic system is unknown. In this study, cholinergic neurons were imaged using PET with 18F-fluoroethoxybenzovesamicol, a radioligand of the vesicular acetylcholine transporter (VAChT). Here, we found an age-related decrease in VAChT expression in the posterior putamen and caudate nucleus of DYT1 patients versus matched controls, with low expression in young but not in older patients. In the cerebellar vermis, VAChT expression was also significantly decreased in patients versus controls, but independently of age. Functional connectivity within the motor network studied in MRI and the interregional correlation of VAChT expression studied in PET were also altered in patients. These results show that the cholinergic system is disrupted in the brain of DYT1 patients and is modulated over time through plasticity or compensatory mechanisms.
摘要
: 早发型扭转肌张力障碍 (TOR1A/DYT1) 是一种严重的遗传性运动功能障碍的病理生理学尚不明确.对转基因小鼠的研究表明壳核中胆碱能传递异常,但这尚未在人类中得到证实。小脑在该疾病的病理生理学中的作用也已被强调,但内在的小脑胆碱能系统的参与是未知的。在这项研究中,使用18f-氟乙氧基苯磺胺 (囊泡乙酰胆碱转运蛋白 (VAChT) 的放射性配体) 的PET对胆碱能神经元进行成像。在这里,我们发现与匹配的对照相比,DYT1患者的后壳核和尾状核中的VAChT表达与年龄相关,年轻患者低表达,但老年患者不表达。在小脑蚓部,患者与对照组相比,VAChT表达也显著降低,但与年龄无关。MRI中研究的运动网络内的功能连接和PET中研究的VAChT表达的区域间相关性也在患者中改变。这些结果表明,胆碱能系统在DYT1患者的脑中被破坏,并且随着时间的推移通过可塑性或代偿机制进行调节。
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