Purpose

Parkinson's disease (PD) is a heterogeneous neurodegenerative disorder, characterized by the dysfunction between dopaminergic and GABAergic neuronal activities. Dopamine (DA) replacement by its precursor L-dopa remains the primary treatment for PD. In this preliminary study, we test the hypotheses that GABA+ levels would be lower in PD patients than controls, and normalized by L-dopa.

Methods

Eleven PD patients and eleven age-and gender-matched healthy controls underwent a ¹H-MRS scan of the upper brainstem using a J-difference-edited sequence to resolve signals of GABA. PD patients did not take all dopaminergic medicines for at least twelve hours prior to the first scan, and were scanned again after resuming L -dopa (pre- and post-L-dopa). MRS data were processed using the Gannet. Differences of GABA+ (GABA, macromolecules, and homocarnosine) levels within-subject (PD: pre- and post-L-dopa) and between-subjects (HC vs. PD-pre or PD-post) were tested using linear mixed-effects models with Holm-Bonferroni correction applied to pairwise comparisons.

Results

Significant increased GABA+ levels were observed in the upper brainstem of PD patients post-L-dopa compared with pre-L-dopa (p < 0.001). Patients' GABA+ levels before administration of L-dopa were significantly lower than HCs (p = 0.001). Increased GABA+ level by administration of L-dopa in PD patients (post-L-dopa) was lower compared with HCs, but not significantly (p = 0.52).

Conclusion

Increased GABA+ levels were present in the upper brainstem with PD patients post-L-dopa, suggesting dopaminergic therapy capable of improving dopamine may improve the GABA+ levels in the upper brainstem, thereby achieving the effect of modulating the GABAergic system in the treatment of PD.

中文翻译：

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初步研究单剂量左旋多巴可增加帕金森氏病上脑干GABA

目的

帕金森氏病（PD）是一种异质性神经退行性疾病，其特征在于多巴胺能和GABA能神经元活动之间的功能障碍。用其前体左旋多巴替代多巴胺（DA）仍然是PD的主要治疗方法。在这项初步研究中，我们测试了以下假设：PD患者的GABA +水平将低于对照组，并通过L-多巴标准化。

方法

11位PD患者以及11位年龄和性别匹配的健康对照者接受了J差异编辑序列对GABA信号进行了¹ H-MRS上脑干扫描。PD患者在第一次扫描之前至少十二小时未服用所有多巴胺能药物，并且在恢复L-多巴（L-多巴之前和之后）后再次进行了扫描。使用Gannet处理MRS数据。使用线性混合效应测试受试者内部（PD：左旋多巴之前和之后）和受试者之间（HC与PD-前或PD-后）的GABA +（GABA，大分子和同型肌肽）水平的差异。 Holm-Bonferroni校正的模型应用于成对比较。

结果

与左旋多巴前相比，左旋多巴后PD患者的上脑干中GABA +水平显着增加（p  <0.001）。左旋多巴给药前患者的GABA +水平显着低于HCs（p  = 0.001）。与HCs相比，PD患者（左L-多巴后）服用L-多巴增加的GABA +水平低于HC，但无统计学意义（p  = 0.52）。

结论

L-多巴后PD患者的上脑干中GABA +水平升高，这表明能够改善多巴胺的多巴胺能疗法可能会改善上脑干中的GABA +水平，从而在治疗PD中达到调节GABA能系统的效果。