Song Yulu, Gong Tao, Xiang Yuanyuan, Mikkelsen Mark, Wang Guangbin, Edden Richard A E
Department of Imaging and Nuclear Medicine, Shandong Medical Imaging Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250021, China.
Department of Neurology, Shandong Province Hospital, Shandong University, Jinan, Shandong 250021, China.
J Neurol Sci. 2021 Mar 15;422:117309. doi: 10.1016/j.jns.2021.117309. Epub 2021 Jan 17.
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.
Eleven PD patients and eleven age-and gender-matched healthy controls underwent a H-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.
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).
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.
帕金森病（PD）是一种异质性神经退行性疾病，其特征在于多巴胺能和γ-氨基丁酸能（GABAergic）神经元活动之间的功能障碍。通过其前体左旋多巴替代多巴胺仍然是PD的主要治疗方法。在这项初步研究中，我们检验以下假设：PD患者的GABA+水平低于对照组，并且左旋多巴可使其恢复正常。
11名PD患者和11名年龄及性别匹配的健康对照者使用J-差异编辑序列对脑桥上部进行氢磁共振波谱（H-MRS）扫描，以解析GABA信号。PD患者在首次扫描前至少12小时未服用所有多巴胺能药物，并在恢复左旋多巴治疗后（左旋多巴治疗前和治疗后）再次进行扫描。MRS数据使用Gannet进行处理。使用线性混合效应模型检验受试者内（PD：左旋多巴治疗前和治疗后）以及受试者间（健康对照与PD-治疗前或PD-治疗后）GABA+（GABA、大分子和高肌肽）水平的差异，并对成对比较应用Holm-Bonferroni校正。
与左旋多巴治疗前相比，PD患者左旋多巴治疗后脑桥上部的GABA+水平显著升高（p < 0.001）。患者在服用左旋多巴之前的GABA+水平显著低于健康对照者（p = 0.001）。PD患者服用左旋多巴后（左旋多巴治疗后）GABA+水平的升高低于健康对照者，但差异不显著（p = 0.52）。
PD患者左旋多巴治疗后脑桥上部的GABA+水平升高，表明能够改善多巴胺的多巴胺能治疗可能会提高脑桥上部的GABA+水平，从而在PD治疗中达到调节GABA能系统的效果。
