Department of Neurology, Affiliated BenQ Hospital of Nanjing Medical University, No. 71, Hexi Street, Jianye District, 210019, Nanjing, Jiangsu, China.
Neurochem Res. 2021 Nov;46(11):3050-3058. doi: 10.1007/s11064-021-03411-0. Epub 2021 Aug 4.
Gut microbiota is closely related to the Parkinson's disease (PD) pathogenesis. Additionally, aggregation of α-synuclein (α-syn) is central to PD pathogenesis. Here we identified the further mechanisms of gut microbiota in PD. A mouse model with PD was established via injection of MPTP. Normal or MPTP-induced PD like animals were treated with FMT from healthy normal mice. Pole test and traction test were performed to examine the effects of FMT on motor function of PD mice. Fecal SCFAs were assessed by gas chromatography-mass spectrometry. The α-syn level in the substantia nigra pars compacta (SN) of mice was measured using western blot. Dopaminergic neurons and microglial activation in the SN were analyzed by immunohistochemistry (IHC) and immunofluorescence (IF) staining. FMT alleviated physical impairment, decreased fecal SCFAs in a mouse model of PD. Additionally, FMT decreased the expression of α-syn, as well as inhibited the activation of microglia in the SN, and blocked the TLR4/PI3K/AKT/NF-κB signaling in the SN and striatum. FMT could protect mice against PD via suppressing α-syn expression and inactivating the TLR4/PI3K/AKT/NF-κB signaling.
肠道微生物群与帕金森病（PD）的发病机制密切相关。此外，α-突触核蛋白（α-syn）的聚集是 PD 发病机制的核心。在这里，我们确定了肠道微生物群在 PD 中的进一步机制。通过注射 MPTP 建立 PD 小鼠模型。用来自健康正常小鼠的 FMT 处理正常或 MPTP 诱导的 PD 样动物。通过 pole 测试和牵引测试检查 FMT 对 PD 小鼠运动功能的影响。通过气相色谱-质谱法评估粪便 SCFAs。使用 Western blot 测量小鼠黑质致密部（SN）中的α-syn 水平。通过免疫组织化学（IHC）和免疫荧光（IF）染色分析 SN 中的多巴胺能神经元和小胶质细胞激活。FMT 减轻了 PD 小鼠的身体损伤，降低了粪便 SCFAs。此外，FMT 降低了 α-syn 的表达，抑制了 SN 中小胶质细胞的激活，并阻断了 SN 和纹状体中的 TLR4/PI3K/AKT/NF-κB 信号。FMT 通过抑制 α-syn 表达和失活 TLR4/PI3K/AKT/NF-κB 信号来保护小鼠免受 PD 的侵害。
