Radboud University Nijmegen, Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging, Nijmegen, The Netherlands.
Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Department of Neurology, Nijmegen, The Netherlands.
Hum Brain Mapp. 2020 Mar;41(4):1017-1029. doi: 10.1002/hbm.24857. Epub 2019 Nov 13.
Parkinson's disease is characterized by bradykinesia, rigidity, and tremor. These symptoms have been related to an increased gamma-aminobutyric acid (GABA)ergic inhibitory drive from globus pallidus onto the thalamus. However, in vivo empirical evidence for the role of GABA in Parkinson's disease is limited. Some discrepancies in the literature may be explained by the presence or absence of tremor. Specifically, recent functional magnetic resonance imaging (fMRI) findings suggest that Parkinson's tremor is associated with reduced, dopamine-dependent thalamic inhibition. Here, we tested the hypothesis that GABA in the thalamocortical motor circuit is increased in Parkinson's disease, and we explored differences between clinical phenotypes. We included 60 Parkinson patients with dopamine-resistant tremor (n = 17), dopamine-responsive tremor (n = 23), or no tremor (n = 20), and healthy controls (n = 22). Using magnetic resonance spectroscopy, we measured GABA-to-total-creatine ratio in motor cortex, thalamus, and a control region (visual cortex) on two separate days (ON and OFF dopaminergic medication). GABA levels were unaltered by Parkinson's disease, clinical phenotype, or medication. However, motor cortex GABA levels were inversely correlated with disease severity, particularly rigidity and tremor, both ON and OFF medication. We conclude that cortical GABA plays a beneficial rather than a detrimental role in Parkinson's disease, and that GABA depletion may contribute to increased motor symptom expression.
帕金森病的特征是运动迟缓、僵硬和震颤。这些症状与苍白球向丘脑的γ-氨基丁酸（GABA）能抑制性驱动增加有关。然而，体内关于 GABA 在帕金森病中作用的实证证据有限。文献中的一些差异可能与震颤的存在或不存在有关。具体来说，最近的功能磁共振成像（fMRI）研究结果表明，帕金森病震颤与多巴胺依赖性丘脑抑制减少有关。在这里，我们检验了以下假设：帕金森病中丘脑皮质运动回路中的 GABA 增加，并且我们探索了临床表型之间的差异。我们纳入了 60 名帕金森病患者，其中有震颤（n = 17）、无震颤（n = 20）和对多巴胺药物有反应的震颤（n = 23），以及健康对照组（n = 22）。使用磁共振波谱，我们在两天（ON 和 OFF 多巴胺药物）测量了运动皮质、丘脑和对照区域（视觉皮质）的 GABA 与总肌酸比。GABA 水平不受帕金森病、临床表型或药物影响。然而，运动皮质 GABA 水平与疾病严重程度呈负相关，尤其是 ON 和 OFF 药物时的僵硬和震颤。我们得出结论，皮质 GABA 在帕金森病中发挥有益作用，而不是有害作用，GABA 耗竭可能导致运动症状表达增加。
