Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, China.
Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine & Health Sciences, Shanghai, China.
Acupunct Med. 2021 Oct;39(5):501-511. doi: 10.1177/0964528421990658. Epub 2021 Feb 8.
Parkinson's disease (PD) is a chronic neurodegenerative disease involving non-motor symptoms, of which gastrointestinal disorders are the most common. In light of recent results, intestinal dysfunction may be involved in the pathogenesis of PD. Electroacupuncture (EA) has shown potential effects, although the underlying mechanism remains mostly unknown. We speculated that EA could relieve the behavioral defects of PD, and that this effect would be associated with modulation of the gut microbiota.
Mice were randomly divided into three groups: control, PD + MA (manual acupuncture), and PD + EA. MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) was used to establish the mouse model of PD. Rotarod performance tests, open field tests, and pole tests were carried out to assess motor deficiencies. Immunohistochemistry was conducted to examine the survival of dopaminergic neurons. 16S ribosomal RNA (rRNA) gene sequencing was applied to investigate the alterations of the gut microbiome. Quantitative real-time polymerase chain reaction (PCR) was performed to characterize the messenger RNA (mRNA) levels of pro-inflammatory and anti-inflammatory cytokines.
We found that EA was able to alleviate the behavioral defects in the rotarod performance test and pole test, and partially rescue the significant loss of dopaminergic neurons in the substantia nigra (SN) chemically induced by MPTP in mice. Moreover, the PD + MA mice showed a tendency toward decreased intestinal microbial alpha diversity, while EA significantly reversed it. The abundance of Erysipelotrichaceae was significantly increased in PD + MA mice, and the alteration was also reversed by EA. In addition, the pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α were substantially increased in the SN of PD + MA mice, an effect that was reversed by EA.
These results suggest that EA may alleviate behavioral defects via modulation of gut microbiota and suppression of inflammation in the SN of mice with PD, which provides new insights into the pathogenesis of PD and its treatment.
帕金森病(PD)是一种慢性神经退行性疾病,涉及非运动症状,其中胃肠道紊乱最为常见。鉴于最近的研究结果,肠道功能障碍可能与 PD 的发病机制有关。电针(EA)已显示出潜在的效果,尽管其潜在机制尚不清楚。我们推测 EA 可以缓解 PD 的行为缺陷,这种效果可能与调节肠道微生物群有关。
将小鼠随机分为三组:对照组、PD+MA(手动针刺)和 PD+EA。使用 1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)建立 PD 小鼠模型。进行转棒性能测试、旷场测试和棒测试以评估运动缺陷。进行免疫组织化学检查以检查多巴胺能神经元的存活情况。16S 核糖体 RNA(rRNA)基因测序用于研究肠道微生物群的变化。实时定量聚合酶链反应(PCR)用于描述促炎和抗炎细胞因子的信使 RNA(mRNA)水平。
我们发现 EA 能够缓解在转棒性能测试和棒测试中的行为缺陷,并部分挽救 MPTP 化学诱导的小鼠黑质(SN)中多巴胺能神经元的显著丧失。此外,PD+MA 小鼠表现出肠道微生物 alpha 多样性降低的趋势,而 EA 则显著逆转了这种趋势。PD+MA 小鼠中 Erysipelotrichaceae 的丰度显著增加,EA 也逆转了这一变化。此外,SN 中促炎细胞因子白细胞介素(IL)-6 和肿瘤坏死因子(TNF)-α的含量在 PD+MA 小鼠中显著增加,EA 逆转了这一作用。
这些结果表明,EA 可能通过调节肠道微生物群和抑制 PD 小鼠 SN 中的炎症来缓解行为缺陷,为 PD 的发病机制及其治疗提供了新的见解。