Subthalamic nucleus deep brain stimulation (STN-DBS) is widely used to treat patients with Parkinson's disease (PD), and recent studies have shown that it is more beneficial for early stages, suggesting a potential neuroprotective effect. And the neuroinflammation plays an indispensable role in progress of PD. However, the underlying mechanisms are not well understood. The aim of this study was to investigate the effect of STN-DBS on neuroinflammation and the potential pathway. To address this question, we established a rat PD model by unilateral 6-hydroxydopamine injection into the left striatum and implanted stimulation leads into the ipsilateral STN to deliver electrical stimulation for a week. The neuroprotective effects of STN-DBS were examined by molecular biology techniques, including western blotting, immunohistochemistry and so on. We found that motor deficits were alleviated by STN-DBS, with increased survival of dopaminergic neurons in the substantia nigra (SN). Furthermore, STN-DBS decreased Fractalkine (CX3CL1) and its receptor (CX3CR1) expression. Meanwhile, the suppressed microglia activation and nuclear factor-κB expression, decrease in the levels of pro-inflammatory cytokine interleukin (IL)-1β and IL-6 and increase in anti-inflammatory cytokine IL-4, downregulated IL-1 receptor, extracellular signal-regulated kinase (ERK) and cleaved-caspase3 were also observed in SN of PD models received STN-DBS. In conclusion, we observed a significant association between the suppressed neuroinflammation and STN-DBS, which may be attributed to CX3CL1/CX3CR1 signaling. These results provide novel insight into the mechanistic basis of STN-DBS therapy for PD.

中文翻译：

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丘脑深部脑刺激通过 Fractalkine 通路抑制帕金森病大鼠模型的神经炎症

丘脑底核深部脑刺激 (STN-DBS) 被广泛用于治疗帕金森病 (PD) 患者，最近的研究表明它对早期更有益，表明具有潜在的神经保护作用。并且神经炎症在PD的进展中起着不可或缺的作用。然而，潜在的机制还不是很清楚。本研究的目的是研究 STN-DBS 对神经炎症和潜在途径的影响。为了解决这个问题，我们通过向左侧纹状体注射单侧 6-羟基多巴胺并植入刺激引线到同侧 STN 以提供一周的电刺激来建立大鼠 PD 模型。STN-DBS的神经保护作用通过分子生物学技术，包括蛋白质印迹、免疫组织化学等进行检验。我们发现 STN-DBS 减轻了运动缺陷，增加了黑质 (SN) 中多巴胺能神经元的存活率。此外，STN-DBS 降低了 Fractalkine (CX3CL1) 及其受体 (CX3CR1) 的表达。同时，抑制小胶质细胞活化和核因子-κB 表达，降低促炎细胞因子白细胞介素 (IL)-1β 和 IL-6 水平，增加抗炎细胞因子 IL-4，下调 IL-1 受体，细胞外在接受 STN-DBS 的 PD 模型的 SN 中也观察到信号调节激酶 (ERK) 和 cleaved-caspase3。总之，我们观察到抑制的神经炎症与 STN-DBS 之间存在显着关联，这可能归因于 CX3CL1/CX3CR1 信号传导。这些结果提供了对 STN-DBS 治疗 PD 的机制基础的新见解。