Division of Brain Sciences, Department of Medicine, Imperial College, London, United Kingdom.
Department of Neurosurgery, Nicklaus Children's Hospital, Miami, Florida, USA; and.
FASEB J. 2019 Jun;33(6):6957-6961. doi: 10.1096/fj.201802628R. Epub 2019 Mar 12.
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is the most commonly used surgical treatment for Parkinson's disease (PD). The disease-modifying aspects of DBS at a cellular level are not fully understood, and the key question of the effect of DBS on the degeneration of the dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) remains to be answered. A major technical hurdle in determining any neuroprotective effect by DBS is its use in mid- to late-stage patients with PD when a majority of the DA neurons have been lost. In this work, we hypothesized that the long-term clinical benefits of DBS are, at least in part, due to a neuromodulatory effect on the SNpc neurons. These changes would affect cellular energetics and mitochondrial metabolism. We examined the number and volume of mitochondria as well as their vicinity to the DA presynaptic terminals postmortem caudate and putamen of 3 healthy individuals, 4 PD cases, and 3 DBS-treated patients. PD seems to have caused an increase in the mean distance between mitochondria and presynaptic terminals as well as a decrease in mean mitochondrial volume and numbers in DA projections. Although there was no difference in distance between mitochondria and presynaptic terminals of SNpc neurons in PD brains DBS-treated brains, DBS treatment seemed to have inhibited or reversed the reduction in mitochondrial volume and numbers caused by PD. These results suggest enhanced metabolic plasticity leading to neuroprotection in the SNpc as a result of STN-DBS.-Mallach, A., Weinert, M., Arthur, J., Gveric, D., Tierney, T. S., Alavian, K. N. examination of Parkinson's disease brains suggests decline in mitochondrial biomass, reversed by deep brain stimulation of subthalamic nucleus.
深部脑刺激（DBS）丘脑底核（STN）是治疗帕金森病（PD）最常用的手术方法。DBS 在细胞水平上的疾病修饰方面尚未完全理解，DBS 对黑质致密部（SNpc）多巴胺能（DA）神经元退化的影响这一关键问题仍有待解答。DBS 具有确定任何神经保护作用的主要技术障碍是，它用于 PD 的中晚期患者，此时大多数 DA 神经元已经丢失。在这项工作中，我们假设 DBS 的长期临床益处至少部分归因于对 SNpc 神经元的神经调节作用。这些变化会影响细胞能量和线粒体代谢。我们检查了 3 名健康个体、4 名 PD 病例和 3 名接受 DBS 治疗的患者死后尾状核和壳核中 DA 突触前末端附近的线粒体数量和体积以及它们的体积。PD 似乎导致线粒体与突触前末端之间的平均距离增加，以及 DA 投射中线粒体体积和数量的平均减少。尽管 PD 大脑中 SNpc 神经元线粒体和突触前末端之间的距离没有差异，但 DBS 治疗似乎抑制或逆转了 PD 引起的线粒体体积和数量的减少。这些结果表明，由于 STN-DBS，SNpc 中的代谢灵活性增强导致了神经保护。
