Department of Neurology, University of Rostock, Gehlsheimer Str. 20, 18147 Rostock, Germany.
Institute of Applied Microelectronics and Computer Engineering, University of Rostock, Albert-Einstein-Str. 26, 18119 Rostock, Germany.
Neurosci Lett. 2023 Sep 25;814:137459. doi: 10.1016/j.neulet.2023.137459. Epub 2023 Aug 23.
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been a highly effective treatment option for mid-to-late-stage Parkinson's disease (PD) for decades. Besides direct effects on brain networks, neuroprotective effects of STN-DBS - potentially via alterations of growth factor expression levels - have been proposed as additional mechanisms of action.
In the context of clarifying DBS mechanisms, we analyzed brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) levels in the basal ganglia, motor and parietal cortices, and dentate gyrus in an animal model of stable, severe dopaminergic deficiency.
We applied one week of continuous unilateral STN-DBS in a group of stable 6-hydroxydopamine (6-OHDA) hemiparkinsonian rats (6-OHDA) in comparison to a 6-OHDA control group (6-OHDA) as well as healthy controls (CTRL and CTRL). BDNF and GDNF levels were determined via ELISAs.
The 6-OHDA lesion did not result in a persistent alteration in either BDNF or GDNF levels in a model of severe dopaminergic deficiency after completion of the dopaminergic degeneration. STN-DBS modestly increased BDNF levels in the entopeduncular nucleus, but even impaired BDNF and GDNF expression in cortical areas.
STN-DBS does not increase growth factor expression when applied to a model of completed, severe dopaminergic deficiency in contrast to other studies in models of modest and ongoing dopaminergic degeneration. In healthy controls, STN-DBS does not influence BDNF or GDNF expression. We consider these findings relevant for clinical purposes since DBS in PD is usually applied late in the course of the disease.
深脑刺激（DBS）的丘脑底核（STN）已成为一种高度有效的治疗选择，为中期至晚期帕金森病（PD）几十年。除了对大脑网络的直接影响，STN-DBS 的神经保护作用 - 可能通过改变生长因子表达水平 - 已被提议作为另外的作用机制。
在阐明 DBS 机制的背景下，我们分析了在稳定的严重多巴胺能缺乏的动物模型中，基底神经节、运动和顶叶皮质和齿状回中的脑源性神经营养因子（BDNF）和胶质细胞源性神经营养因子（GDNF）水平。
我们应用了一周的连续单侧 STN-DBS 在一组稳定的 6-羟多巴胺（6-OHDA）半帕金森大鼠（6-OHDA）与 6-OHDA 对照组（6-OHDA）以及健康对照组（CTRL 和 CTRL）进行比较。BDNF 和 GDNF 水平通过 ELISA 确定。
6-OHDA 损伤在完成多巴胺能变性后，在严重多巴胺能缺乏的模型中，BDNF 或 GDNF 水平没有持续改变。STN-DBS 适度增加了红核脚间核中的 BDNF 水平，但即使在皮质区域也损害了 BDNF 和 GDNF 的表达。
与其他在适度和持续多巴胺能变性模型中的研究相反，STN-DBS 在应用于完成的严重多巴胺能缺乏模型时不会增加生长因子的表达。在健康对照组中，STN-DBS 不影响 BDNF 或 GDNF 的表达。我们认为这些发现与临床目的有关，因为 PD 中的 DBS 通常在疾病的晚期应用。
