High frequency stimulation of subthalamic nucleus results in behavioral recovery by increasing striatal dopamine release in 6-hydroxydopamine lesioned rat
High frequency stimulation of subthalamic nucleus results in behavioral recovery by increasing striatal dopamine release in 6-hydroxydopamine lesioned rat
复制标题
高频刺激底丘脑核通过增加 6-羟基多巴胺损伤大鼠纹状体多巴胺释放导致行为恢复
DOI：
10.1016/j.bbr.2014.01.014
复制
发表时间：
2014-04-15
影响因子：
2.7
通讯作者：
Xie, Junxia
中科院分区：
文献类型：
--
作者：
He, Zheng;Jiang, Yunxia;Xie, Junxia
丘脑底核深部脑刺激(DBS)是缓解中重度帕金森病(PD)患者运动症状的有效药物疗法。然而，关于这一行动的机制仍然存在疑问。本实验采用6-羟基多巴胺(6-OHDA)帕金森病大鼠模型，观察高频刺激(HFS)-STN对帕金森病大鼠运动症状的改善及纹状体DA释放的影响，并探讨其作用机制。结果表明，HFS-STN通过诱导正常大鼠和部分6-OHDA损毁大鼠纹状体内细胞外多巴胺水平显着升高和直接诱发多巴胺释放，改善帕金森病模型大鼠的运动症状。此外，我们还发现HFS-STN后黑质致密部(SNPC)的酪氨酸羟化酶(TH)阳性细胞数没有增加，而黑质TH的表达与6-OHDA损伤组相比显著增加。提示STN-HFS可通过调节TH的表达来增加纹状体多巴胺的释放，而不挽救SNPC内的多巴胺能神经元，从而逆转6-OHDA所致损伤的运动障碍。(C)2014爱思唯尔B.V.保留所有权利。
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective medical therapy in alleviating motor symptoms in moderate to severe Parkinson's disease (PD) patients. However, there are still remaining questions regarding the mechanisms of this action. In this experiment, using 6-hydroxydopamine (6-OHDA) PD rat model we investigated the effect of high frequency stimulation (HFS)-STN on improvement of the motor symptoms, DA release in the striatum and to elucidate the underlying mechanisms. Our results showed that HFS-STN improved the motor symptoms of 6-OHDA lesioned rat model of PD via inducing a significant increase in the extracellular dopamine levels and directly evoked dopamine release in the striatum of normal and partially 6-OHDA lesioned rats. In addition, we found the tyrosine hydroxylase (TH) positive cells in the substantia nigra pars compacta (SNpc) did not increase after HFS-STN, while the expression of TH in the substantia nigra increased significantly compared to the 6-OHDA lesioned group. This suggested that STN-HFS could reverse motor deficits against 6-OHDA-induced lesion through increasing striatal dopamine release by modulating the expression of TH, without rescuing dopaminergic neurons in the SNpc. (C) 2014 Elsevier B.V. All rights reserved.