Department of Anesthesiology, Yangzhi Rehabilitation Hospital Affiliated to Tongji University, School of Medicine, Tongji University, Shanghai, China; Department of Anesthesiology, Tongji Hospital Affiliated to Tongji University, School of Medicine, Tongji University, Shanghai, China.
Department of Anesthesiology, Yangzhi Rehabilitation Hospital Affiliated to Tongji University, School of Medicine, Tongji University, Shanghai, China.
Neurochem Int. 2024 Nov;180:105871. doi: 10.1016/j.neuint.2024.105871. Epub 2024 Oct 1.
Parkinson's disease (PD) is a common neurodegenerative disease characterized by the loss of dopaminergic (DA) neurons in the substantia nigra (SN). Conventional treatments are ineffective in reversing disease progression. Recently, the therapeutic and rehabilitation potential of vagus nerve stimulation (VNS) in PD has been explored. However, the underlying mechanisms remain largely unknown. In this study, we investigated the neuroprotective effects of VNS in a lateral lesioned mice model of PD. Excluding controls, experimental mice received cuff electrode implantation on the left vagus nerve and 6-hydroxydopamine administration into the bilateral striatum. After ten days, electrical stimulation was delivered for 11 consecutive days onto PD animals. Behavioral tests were performed after stimulation. The expression of TH, Iba-1, GFAP, adrenergic receptors and cytokines in the SN and striatum was detected by immunofluorescence or western blotting. The activity of noradrenergic neurons in the locus coeruleus (LC) was also measured. Our results suggest that VNS improved behavioral performance in rod rotation, open field tests and pole-climbing tests in PD mice, accompanied by a decrease in the loss of dopaminergic neurons in the SN and increased TH expression in the striatum. Neuroinflammation-related factors, such as GFAP, Iba-1, TNF-α and IL-1β were also suppressed in PD mice after VNS compared to those without treatment. Furthermore, the proportion of c-Fos-positive noradrenergic neurons in the LC increased when animals received VNS. Additionally, the expression of the adrenergic receptor of α1BR was also upregulated after VNS compared to PD mice. In conclusion, VNS has potential as a novel PD therapy for neuroprotective effects, and indicate that activation of norepinephric neurons in LC may plays an important role in VNS treatment for PD.
帕金森病（PD）是一种常见的神经退行性疾病，其特征是黑质（SN）中的多巴胺能（DA）神经元丧失。传统的治疗方法在逆转疾病进展方面效果不佳。最近，迷走神经刺激（VNS）在 PD 中的治疗和康复潜力已被探索。然而，其潜在机制在很大程度上仍不清楚。在这项研究中，我们研究了 VNS 在 PD 的外侧损伤小鼠模型中的神经保护作用。除对照组外，实验小鼠的左侧迷走神经接受袖带电极植入，双侧纹状体接受 6-羟多巴胺处理。十天后，对 PD 动物进行了连续 11 天的电刺激。刺激后进行行为测试。通过免疫荧光或 Western blot 检测 SN 和纹状体中 TH、Iba-1、GFAP、肾上腺素能受体和细胞因子的表达。还测量了蓝斑核（LC）中的去甲肾上腺素能神经元的活性。我们的结果表明，VNS 改善了 PD 小鼠在旋转棒、旷场试验和爬杆试验中的行为表现，同时减少了 SN 中多巴胺能神经元的丢失，并增加了纹状体中的 TH 表达。与未经治疗的 PD 小鼠相比，VNS 后 PD 小鼠中的神经炎症相关因子，如 GFAP、Iba-1、TNF-α和 IL-1β也减少。此外，当动物接受 VNS 时，LC 中 c-Fos 阳性去甲肾上腺素能神经元的比例增加。此外，与 PD 小鼠相比，VNS 后 α1BR 肾上腺素能受体的表达也上调。总之，VNS 作为一种新的 PD 治疗方法具有神经保护作用，表明 LC 中去甲肾上腺素能神经元的激活可能在 VNS 治疗 PD 中发挥重要作用。
