Melon Christophe, Chassain Carine, Bielicki Guy, Renou Jean-Pierre, Kerkerian-Le Goff Lydia, Salin Pascal, Durif Franck
Aix Marseille Université, CNRS, IBDM UMR 7288, Marseille, France.
J Neurochem. 2015 Mar;132(6):703-12. doi: 10.1111/jnc.13015. Epub 2015 Feb 12.
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an efficient neurosurgical treatment for advanced Parkinson's disease. Non-invasive metabolic neuroimaging during the course of DBS in animal models may contribute to our understanding of its action mechanisms. Here, DBS was adapted to in vivo proton magnetic resonance spectroscopy at 11.7 T in the rat to follow metabolic changes in main basal ganglia structures, the striatum, and the substantia nigra pars reticulata (SNr). Measurements were repeated OFF and ON acute and subchronic (7 days) STN-DBS in control and parkinsonian (6-hydroxydopamine lesion) conditions. Acute DBS reversed the increases in glutamate, glutamine, and GABA levels induced by the dopamine lesion in the striatum but not in the SNr. Subchronic DBS normalized GABA in both the striatum and SNr, and glutamate in the striatum. Taurine levels were markedly decreased under subchronic DBS in the striatum and SNr in both lesioned and unlesioned rats. Microdialysis in the striatum further showed that extracellular taurine was increased. These data reveal that STN-DBS has duration-dependent metabolic effects in the basal ganglia, consistent with development of adaptive mechanisms. In addition to counteracting defects induced by the dopamine lesion, prolonged DBS has proper effects independent of the pathological condition. Non-invasive metabolic neuroimaging might be useful to understand the physiological mechanisms of deep brain stimulation (DBS). Here, we demonstrate the feasibility of repeated high-field proton magnetic resonance spectroscopy of basal ganglia structures under subthalamic nucleus DBS in control and parkinsonian rats. Results show that DBS has both rapid and delayed effects either dependent or independent of disease state.
丘脑底核（STN）的深部脑刺激（DBS）是治疗晚期帕金森病的一种有效神经外科治疗方法。在动物模型的DBS过程中进行非侵入性代谢神经成像可能有助于我们理解其作用机制。在此，将DBS应用于大鼠11.7 T的体内质子磁共振波谱，以跟踪主要基底神经节结构、纹状体和黑质网状部（SNr）的代谢变化。在对照和帕金森病（6-羟基多巴胺损伤）条件下，分别在急性和亚慢性（7天）STN-DBS开启和关闭时重复进行测量。急性DBS可逆转多巴胺损伤诱导的纹状体中谷氨酸、谷氨酰胺和GABA水平的升高，但在SNr中则不能。亚慢性DBS使纹状体和SNr中的GABA以及纹状体中的谷氨酸水平恢复正常。在亚慢性DBS下，损伤和未损伤大鼠的纹状体和SNr中的牛磺酸水平均显著降低。纹状体中的微透析进一步表明细胞外牛磺酸增加。这些数据表明，STN-DBS在基底神经节中具有持续时间依赖性的代谢作用，这与适应性机制的发展一致。除了抵消多巴胺损伤引起的缺陷外，长期DBS具有独立于病理状况的适当作用。非侵入性代谢神经成像可能有助于理解深部脑刺激（DBS）的生理机制。在此，我们证明了在对照和帕金森病大鼠的丘脑底核DBS下对基底神经节结构进行重复高场质子磁共振波谱的可行性。结果表明，DBS具有依赖或独立于疾病状态的快速和延迟效应。
