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Altered urinary tetrahydroisoquinoline derivatives in patients with Tourette syndrome: reflection of dopaminergic hyperactivity?
Journal of Neural Transmission ( IF 3.2 ) Pub Date : 2020-12-23 , DOI: 10.1007/s00702-020-02289-6
Philipp Capetian 1 , Veit Roessner 2 , Caroline Korte 3 , Susanne Walitza 4 , Franz Riederer 5, 6 , Regina Taurines 7 , Manfred Gerlach 7 , Andreas Moser 3
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Tetrahydroisoquinolines (TIQs) such as salsolinol (SAL), norsalsolinol (NSAL) and their methylated derivatives N-methyl-norsalsolinol (NMNSAL) and N-methyl-salsolinol (NMSAL), modulate dopaminergic neurotransmission and metabolism in the central nervous system. Dopaminergic neurotransmission is thought to play an important role in the pathophysiology of chronic tic disorders, such as Tourette syndrome (TS). Therefore, the urinary concentrations of these TIQ derivatives were measured in patients with TS and patients with comorbid attention-deficit/hyperactivity disorder (TS + ADHD) compared with controls. Seventeen patients with TS, 12 with TS and ADHD, and 19 age-matched healthy controls with no medication took part in this study. Free levels of NSAL, NMNSAL, SAL, and NMSAL in urine were measured by a two-phase chromatographic approach. Furthermore, individual TIQ concentrations in TS patients were used in receiver-operating characteristics (ROC) curve analysis to examine the diagnostic value. NSAL concentrations were elevated significantly in TS [434.67 ± 55.4 nmol/l (standard error of mean = S.E.M.), two-way ANOVA, p < 0.0001] and TS + ADHD patients [605.18 ± 170.21 nmol/l (S.E.M.), two-way ANOVA, p < 0.0001] compared with controls [107.02 ± 33.18 nmol/l (S.E.M.), two-way ANOVA, p < 0.0001] and NSAL levels in TS + ADHD patients were elevated significantly in comparison with TS patients (two-way ANOVA, p = 0.017). NSAL demonstrated an AUC of 0.93 ± 0.046 (S.E.M) the highest diagnostic value of all metabolites for the diagnosis of TS. Our results suggest a dopaminergic hyperactivity underlying the pathophysiology of TS and ADHD. In addition, NSAL concentrations in urine may be a potential diagnostic biomarker of TS.



中文翻译:

图雷特综合征患者尿四氢异喹啉衍生物的改变:多巴胺能亢进的反映?

四氢异喹啉 (TIQs),例如 salsolinol (SAL)、norsalsolinol (NSAL) 及其甲基化衍生物 N-甲基-norsalsolinol (NMNSAL) 和N-methyl-salsolinol (NMSAL),调节中枢神经系统中的多巴胺能神经传递和代谢。多巴胺能神经传递被认为在慢性抽动障碍的病理生理学中起重要作用,例如图雷特综合征 (TS)。因此,与对照组相比,在 TS 患者和合并注意力缺陷/多动障碍 (TS + ADHD) 患者中测量了这些 TIQ 衍生物的尿浓度。17 名 TS 患者、12 名 TS 和 ADHD 患者以及 19 名年龄匹配且未服用药物的健康对照者参加了这项研究。通过两相色谱法测量尿液中游离的 NSAL、NMNSAL、SAL 和 NMSAL 水平。此外,将 TS 患者的个体 TIQ 浓度用于接受者操作特征 (ROC) 曲线分析以检查诊断价值。p  < 0.0001] 和 TS + ADHD 患者 [605.18 ± 170.21 nmol/l (SEM),双向 ANOVA,p  < 0.0001] 与对照组 [107.02 ± 33.18 nmol/l (SEM),双向 ANOVA,p  < 0.0001] 和 TS + ADHD 患者的 NSAL 水平与 TS 患者相比显着升高(双向 ANOVA,p  = 0.017)。NSAL 的 AUC 为 0.93 ± 0.046 (SEM),是所有代谢物诊断 TS 的最高诊断价值。我们的研究结果表明多巴胺能亢进是 TS 和 ADHD 病理生理学的基础。此外,尿液中的 NSAL 浓度可能是 TS 的潜在诊断生物标志物。

更新日期:2020-12-23
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