School of Public Health and Management, Chongqing Medical University, 1 Yi Xue Yuan Road, Chongqing, 400016, People's Republic of China.
School of Basic Medicine, Chongqing Medical University, Chongqing, 400016, People's Republic of China.
Neurochem Res. 2018 Oct;43(10):1986-1999. doi: 10.1007/s11064-018-2620-x. Epub 2018 Aug 31.
Patients with Parkinson's disease (PD) often have non-motor symptoms related to gastrointestinal (GI) dysfunction, such as constipation and delayed gastric emptying, which manifest prior to the motor symptoms of PD. Increasing evidence indicates that changes in the composition of the gut microbiota may be related to the pathogenesis of PD. However, it is unclear how GI dysfunction occurs and how gut microbial dysbiosis is caused. We investigated whether a neurotoxin model of PD induced by chronic low doses of MPTP is capable of reproducing the clinical intestinal pathology of PD, as well as whether gut microbial dysbiosis accompanies this pathology. C57BL/6 male mice were administered 18 mg/kg MPTP twice per week for 5 weeks via intraperitoneal injection. GI function was assessed by measuring the 1-h stool frequency and fecal water content; motor function was assessed by pole tests; and tyrosine hydroxylase and alpha-synuclein expression were analyzed. Furthermore, the inflammation, intestinal barrier and composition of the gut microbiota were measured. We found that MPTP caused GI dysfunction and intestinal pathology prior to motor dysfunction. The composition of the gut microbiota was changed; in particular, the change in the abundance of Lachnospiraceae, Erysipelotrichaceae, Prevotellaceae, Clostridiales, Erysipelotrichales and Proteobacteria was significant. These results indicate that a chronic low-dose MPTP model can be used to evaluate the progression of intestinal pathology and gut microbiota dysbiosis in the early stage of PD, which may provide new insights into the pathogenesis of PD.
帕金森病（PD）患者常伴有与胃肠道（GI）功能障碍相关的非运动症状，如便秘和胃排空延迟，这些症状先于 PD 的运动症状出现。越来越多的证据表明，肠道微生物群落组成的改变可能与 PD 的发病机制有关。然而，目前尚不清楚 GI 功能障碍是如何发生的，以及肠道微生物失调是如何引起的。我们研究了慢性低剂量 MPTP 诱导的 PD 神经毒素模型是否能够重现 PD 的临床肠道病理学，以及肠道微生物失调是否伴随着这种病理学。通过腹腔注射，每周两次给 C57BL/6 雄性小鼠施用 18mg/kg MPTP，共 5 周。通过测量 1 小时粪便频率和粪便含水量来评估 GI 功能；通过杆试验评估运动功能；并分析酪氨酸羟化酶和α-突触核蛋白的表达。此外，还测量了炎症、肠道屏障和肠道微生物群落的组成。我们发现，MPTP 在运动功能障碍之前导致了 GI 功能障碍和肠道病理学。肠道微生物群落的组成发生了改变；特别是 Lachnospiraceae、Erysipelotrichaceae、Prevotellaceae、Clostridiales、Erysipelotrichales 和 Proteobacteria 的丰度变化显著。这些结果表明，慢性低剂量 MPTP 模型可用于评估 PD 早期肠道病理学和肠道微生物失调的进展，这可能为 PD 的发病机制提供新的见解。
