■脑深部电刺激(DBS)是治疗帕金森病的一种非常有效的选择。然而,潜在的行动机制,特别是对神经元可塑性的影响,仍然神秘。脑室下区-嗅球(SVZ-OB)轴和齿状回(DG)中的成人神经发生与PD中的各种非运动症状有关,例如,记忆障碍和嗅觉功能障碍。由于DBS会影响这些非运动症状中的几种,我们分析了丘脑底核(STN)和足核(EPN)中DBS对6-羟基多巴胺(6-OHDA)损伤的半帕金森病大鼠神经发生的影响。
■在我们的研究中,我们在多巴胺能缺陷稳定的6-OHDA损伤大鼠中应用了为期五周的连续双侧STN-DBS或EPN-DBS,而6-OHDA损伤大鼠具有相应的假刺激。我们注射了两种胸苷类似物,以在DBS发作后早期和三周后定量新生神经元。免疫组织化学鉴定了与NeuN共同标记的新生细胞,OB和DG内的TH和GABA。作为一种推定机制,我们模拟了不同刺激部位的电场分布,分析了电对神经干细胞增殖的直接影响。
■STN-DBS持续增加OB中新生多巴胺能和GABA能神经元的数量,而DG中没有,而EPN-DBS不影响神经发生。这些作用似乎不是通过直接电刺激神经源性壁ni内的神经干/祖细胞介导的。
■我们的数据支持STN-DBS对成人神经发生的靶标特异性作用,帕金森病非运动症状的推定调节剂。
UNASSIGNED: Deep brain stimulation (DBS) is a highly effective treatment option in Parkinson\'s disease. However, the underlying mechanisms of action, particularly effects on neuronal plasticity, remain enigmatic. Adult neurogenesis in the subventricular zone-olfactory bulb (SVZ-OB) axis and in the dentate gyrus (DG) has been linked to various non-motor symptoms in PD, e.g., memory deficits and olfactory dysfunction. Since DBS affects several of these non-motor symptoms, we analyzed the effects of DBS in the subthalamic nucleus (STN) and the entopeduncular nucleus (EPN) on neurogenesis in 6-hydroxydopamine (6-OHDA)-lesioned hemiparkinsonian rats.
UNASSIGNED: In our study, we applied five weeks of continuous bilateral STN-DBS or EPN-DBS in 6-OHDA-lesioned rats with stable dopaminergic deficits compared to 6-OHDA-lesioned rats with corresponding sham stimulation. We injected two thymidine analogs to quantify newborn neurons early after DBS onset and three weeks later. Immunohistochemistry identified newborn cells co-labeled with NeuN, TH and GABA within the OB and DG. As a putative mechanism, we simulated the electric field distribution depending on the stimulation site to analyze direct electric effects on neural stem cell proliferation.
UNASSIGNED: STN-DBS persistently increased the number of newborn dopaminergic and GABAergic neurons in the OB but not in the DG, while EPN-DBS does not impact neurogenesis. These effects do not seem to be mediated via direct electric stimulation of neural stem/progenitor cells within the neurogenic niches.
UNASSIGNED: Our data support target-specific effects of STN-DBS on adult neurogenesis, a putative modulator of non-motor symptoms in Parkinson\'s disease.