Bruet N, Windels F, Bertrand A, Feuerstein C, Poupard A, Savasta M
Equipe Neurochimie et Neuroplasticité Fonctionnelles, INSERM U.318--Neurosciences Précliniques, Université Joseph Fourier, Pavillon de Neurologie, CHU de Grenoble, France.
J Neuropathol Exp Neurol. 2001 Jan;60(1):15-24. doi: 10.1093/jnen/60.1.15.
The subthalamic nucleus (STN) has come under focus in Parkinson disease (PD) because of recent advances in the understanding of the functional organization of the basal ganglia in normal and pathological conditions. Manipulations of the STN have been described to compensate for some imbalance in motor output of the basal ganglia in animal models of PD and have been proposed as a potential therapeutic target in humans. Indeed, high frequency stimulation (HFS) (130 Hz) of the STN has beneficial effects in severe parkinsonian patients but the precise mechanisms underlying these clinical results remain to be elucidated. To date, very little is known concerning the effect of HFS-STN on striatal dopaminergic transmission. Since it has been reported that dopaminergic medication may be reduced in PD patients under HFS-STN, our goal was to study the effect of HFS-STN on striatal dopamine (DA) transmission by using intracerebral microdialysis in normal and partially DA denervated rats. Our results show that HFS STN induces a significant increase of extracellular DA in the striatum of normal and partially DA lesioned rats while striatal extracellular levels of DOPAC were not affected. We conclude that HFS-STN acts directly and/or indirectly on striatal DA levels in control or partially DA lesioned rats.
由于在正常和病理条件下对基底神经节功能组织的理解取得了最新进展，丘脑底核（STN）已成为帕金森病（PD）研究的焦点。在帕金森病动物模型中，对丘脑底核的操作已被描述为可补偿基底神经节运动输出的某些失衡，并已被提议作为人类的潜在治疗靶点。事实上，对丘脑底核进行高频刺激（HFS）（130Hz）对重度帕金森病患者具有有益效果，但这些临床结果背后的确切机制仍有待阐明。迄今为止，关于高频刺激丘脑底核对纹状体多巴胺能传递的影响知之甚少。由于有报道称，接受高频刺激丘脑底核治疗的帕金森病患者可能会减少多巴胺能药物的使用，我们的目标是通过在正常和部分多巴胺去神经支配的大鼠中使用脑内微透析技术，研究高频刺激丘脑底核对纹状体多巴胺（DA）传递的影响。我们的结果表明，高频刺激丘脑底核可导致正常和部分多巴胺损伤大鼠纹状体中细胞外多巴胺显著增加，而纹状体中3,4-二羟基苯乙酸（DOPAC）的细胞外水平不受影响。我们得出结论，高频刺激丘脑底核直接和/或间接作用于对照或部分多巴胺损伤大鼠的纹状体多巴胺水平。
