Roussakis Andreas-Antonios, Politis Marios, Towey David, Piccini Paola
From the Neurology Imaging Unit (A.-A.R., P.P.), Centre of Neuroinflammation and Neurodegeneration, Division of Brain Sciences, Hammersmith Campus, Imperial College London; Neurodegeneration Imaging Group (M.P.), Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London; and Radiological Sciences Unit (D.T.), Imperial College Healthcare NHS Trust, London, UK.
Neurology. 2016 Mar 22;86(12):1152-8. doi: 10.1212/WNL.0000000000002494. Epub 2016 Feb 26.
To investigate whether a serotonin-to-dopamine terminal ratio is related to the appearance of dyskinesias in patients with Parkinson disease (PD).
Twenty-eight patients with idiopathic PD (17 with levodopa-induced dyskinesias [LIDs], 11 without dyskinesias) and 12 age-matched healthy controls were studied with PET and 5[(11)C]-3-amino-4-(2-dimethylaminomethylphenyl-sulfanyl)-benzonitrile ((11)C-DASB) and with SPECT and [(123)I]N-w-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane ((123)I-ioflupane), which are in vivo specific markers of the serotonin and dopamine transporters' availability, respectively. We have employed a simplified reference tissue model for the quantification of (11)C-DASB, whereas a semiquantification approach was used for (123)I-ioflupane data. We calculated (11)C-DASB binding to (123)I-ioflupane uptake ratios for the caudate and the putamen.
Patients with PD showed striatal decreases in (11)C-DASB binding potential (p < 0.01) and in (123)I-ioflupane mean uptake (p < 0.001) compared to controls. The mean (11)C-DASB binding to (123)I-ioflupane uptake ratio in the putamen was 0.779 (increased by 75.8% of the controls' mean) for the nondyskinetic group and 0.901 (increased by 103.4% of the controls' mean) for the patients with dyskinesias. There was a statistically significant difference (p < 0.001) in (11)C-DASB binding to (123)I-ioflupane uptake ratio in the putamen between the group of patients with and without dyskinesias. Higher (11)C-DASB to (123)I-ioflupane binding ratios correlated with longer disease duration for the 28 patients with PD (r = 0.52; p < 0.01).
Serotonin-to-dopamine transporter binding ratio increases as PD progresses and patients experience LIDs. Our findings suggest that, when the dopaminergic innervation in the striatum is critically low, the serotonergic system plays an important role in development of LIDs.
研究帕金森病（PD）患者中5-羟色胺与多巴胺终末比值是否与运动障碍的出现有关。
对28例特发性PD患者（17例有左旋多巴诱导的运动障碍[LIDs]，11例无运动障碍）和12例年龄匹配的健康对照者进行正电子发射断层扫描（PET）及5-[(11)C]-3-氨基-4-(2-二甲基氨基甲基苯基硫烷基)-苯甲腈（(11)C-DASB）检查，以及单光子发射计算机断层扫描（SPECT）及[(123)I]N-w-氟丙基-2β-甲氧基羰基-3β-(4-碘苯基)去甲托烷（(123)I-碘氟潘）检查，这两种检查分别是5-羟色胺和多巴胺转运体可用性的体内特异性标志物。我们采用简化参考组织模型对(11)C-DASB进行定量分析，而对(123)I-碘氟潘数据采用半定量方法。我们计算了尾状核和壳核的(11)C-DASB结合与(123)I-碘氟潘摄取比值。
与对照组相比，PD患者纹状体中(11)C-DASB结合潜能降低（p<0.01），(123)I-碘氟潘平均摄取降低（p<0.001）。无运动障碍组壳核中(11)C-DASB结合与(123)I-碘氟潘摄取的平均比值为0.779（比对照组平均值增加75.8%），有运动障碍患者为0.901（比对照组平均值增加103.4%）。有运动障碍和无运动障碍患者组之间壳核中(11)C-DASB结合与(123)I-碘氟潘摄取比值存在统计学显著差异（p<0.001）。对于28例PD患者，较高的(11)C-DASB与(123)I-碘氟潘结合比值与疾病持续时间较长相关（r=0.52；p<0.01）。
随着PD进展及患者出现LIDs，5-羟色胺与多巴胺转运体结合比值升高。我们的研究结果表明，当纹状体中多巴胺能神经支配严重不足时，5-羟色胺能系统在LIDs的发生中起重要作用。
