Li Tianlang, Qadri Fatimunnisa, Moser Andreas
School of Medicine, Second Affiliated Hospital of Zhejiang University, Hangzhou, PR China.
Neurosci Lett. 2004 Nov 23;371(2-3):117-21. doi: 10.1016/j.neulet.2004.08.050.
Electrical high frequency deep brain stimulation (DBS) of the globus pallidus internus (GPi) or the subthalamic nucleus (STN) has dramatic beneficial motor effects in advanced Parkinson's disease (PD). However, the mechanisms underlying these clinical results remain unclear. It is proposed that the gamma-aminobutyric acid (GABA) system is involved in the effectiveness of DBS. To prove this hypothesis, rat striatal slices were stimulated electrically (130 Hz) in vitro; GABA and glutamate (GLU) outflow from striatal slices of normal or kainic acid-lesioned rats were measured after o-phthaldialdehyde sulphite derivatization using HPLC with electrochemical detection. Our results could demonstrate that high frequency stimulation (HFS) did not modulate basal GABA outflow in the perfusate. In the presence of submaximal concentrations of the voltage-gated sodium channel opener veratridine, HFS significantly enhanced GABA outflow. When the GABA transporter inhibitor, nipecotic acid, was added to the incubation medium, the HFS effects decreased to nearly control values. Destruction of striatal GABAergic neurons by kainic acid completely reversed the effects of HFS on GABA outflow. In the present study no effect of HFS on glutamate outflow was observed under any condition. These results suggest that HFS has a specific effect on GABAergic neuronal terminals resulting in an enhancement of extracellular GABA in the caudate nucleus. This effect is probably due to an inhibitory effect of HFS on the GABA uptake system rather than to stimulation of vesicular GABA release from GABAergic neurons, which are both associated with the presynaptic GABAergic physiology.
对苍白球内侧部（GPi）或丘脑底核（STN）进行高频深部脑刺激（DBS）对晚期帕金森病（PD）具有显著的有益运动效果。然而，这些临床结果背后的机制仍不清楚。有人提出γ-氨基丁酸（GABA）系统参与了DBS的有效性。为了验证这一假设，在体外对大鼠纹状体切片进行电刺激（130Hz）；使用高效液相色谱电化学检测法，在邻苯二甲醛亚硫酸盐衍生化后，测量正常或 kainic 酸损伤大鼠纹状体切片中 GABA 和谷氨酸（GLU）的流出量。我们的结果表明高频刺激（HFS）并未调节灌注液中基础 GABA 的流出。在存在亚最大浓度的电压门控钠通道开放剂藜芦碱的情况下，HFS 显著增强了 GABA 的流出。当将 GABA 转运体抑制剂尼克酸添加到孵育培养基中时，HFS 的作用降低到接近对照值。用 kainic 酸破坏纹状体 GABA 能神经元完全逆转了 HFS 对 GABA 流出的影响。在本研究中，在任何条件下均未观察到 HFS 对谷氨酸流出的影响。这些结果表明，HFS 对 GABA 能神经元终末具有特异性作用，导致尾状核细胞外 GABA 增加。这种作用可能是由于 HFS 对 GABA 摄取系统的抑制作用，而不是对 GABA 能神经元囊泡 GABA 释放的刺激作用，这两者均与突触前 GABA 能生理学相关。
