Center for MR Research, University Children's Hospital Zurich, Steinwiesstrasse 75, Zurich, 8032, Switzerland.
Department of Neurology, University Hospital Zurich, Frauenklinikstrasse 26, Zurich, 8091, Switzerland.
Parkinsonism Relat Disord. 2018 May;50:54-60. doi: 10.1016/j.parkreldis.2018.02.014. Epub 2018 Feb 8.
While the mechanisms underlying the therapeutic effects of deep brain stimulation (DBS) in Parkinson's Disease (PD) are not yet fully understood, DBS appears to exert a wide range of neurochemical effects on the network level, thought to arise from activation of inhibitory and excitatory pathways. The activity within the primary inhibitory (GABAergic) and excitatory (glutamatergic) neurotransmitter systems may therefore play an important role in the therapeutic efficacy of DBS in PD. The purpose of this study was to investigate abnormalities in GABA-ergic and glutamatergic neurotransmission in PD, and to examine the link between neurotransmitter levels and outcome following DBS.
Magnetic resonance spectra were acquired from the pons and basal ganglia in sixteen patients with PD and sixteen matched control participants. GABA and glutamate levels were quantified with LCModel, an automated spectral fitting package. Fourteen patients subsequently underwent DBS, and PD symptoms were evaluated with the MDS-UPDRS at baseline and six months after surgery. The efficacy of DBS treatment was evaluated from the percentage improvement in MDS-UPDRS scores.
Basal ganglia GABA levels were significantly higher in PD patients relative to control participants (p < 0.01), while pontine glutamate + glutamine (Glx) levels were significantly lower in patients with PD (p < 0.05). While GABA levels were not significantly related to outcome post-surgery, basal ganglia glutamate levels emerged as a significant predictor of outcome, suggesting a possible role for glutamatergic neurotransmission in the therapeutic mechanism of DBS.
GABAergic and glutamatergic neurotransmission is altered in PD, and glutamatergic activity in particular may influence outcome post-surgery.
尽管深部脑刺激（DBS）治疗帕金森病（PD）的机制尚未完全阐明，但 DBS 似乎对网络水平产生广泛的神经化学影响，据认为这是通过激活抑制性和兴奋性途径产生的。因此，初级抑制性（GABA 能）和兴奋性（谷氨酸能）神经递质系统内的活动可能在 DBS 治疗 PD 的疗效中发挥重要作用。本研究旨在研究 PD 中 GABA 能和谷氨酸能神经传递的异常，并探讨神经递质水平与 DBS 后结果之间的联系。
从 16 名 PD 患者和 16 名匹配的对照参与者的脑桥和基底节采集磁共振谱。使用 LCModel（一种自动光谱拟合软件包）定量测定 GABA 和谷氨酸水平。随后，14 名患者接受了 DBS，并且在基线和手术后六个月使用 MDS-UPDRS 评估 PD 症状。从 MDS-UPDRS 评分的百分比改善来评估 DBS 治疗的效果。
与对照参与者相比，PD 患者的基底节 GABA 水平显著升高（p < 0.01），而 PD 患者的脑桥谷氨酸+谷氨酰胺（Glx）水平显著降低（p < 0.05）。尽管 GABA 水平与术后结果无显著相关性，但基底节谷氨酸水平成为结果的显著预测因素，表明谷氨酸能神经传递可能在 DBS 的治疗机制中发挥作用。
PD 中 GABA 能和谷氨酸能神经传递发生改变，特别是谷氨酸能活性可能影响术后结果。
