Fecal Microbiota Transplantation Exerts a Protective Role in MPTP-Induced Parkinson’s Disease via the TLR4/PI3K/AKT/NF-κB Pathway Stimulated by α-Synuclein

被引:0
作者
Zhe Zhong
Weijie Chen
Huan Gao
Ningning Che
Min Xu
Lanqing Yang
Yingfang Zhang
Min Ye
机构
[1] Affiliated BenQ Hospital of Nanjing Medical University,Department of Neurology
来源
Neurochemical Research | 2021年 / 46卷
关键词
Gut microbiota; Parkinson's disease; α-synuclein; TLR4/PI3K/AKT/NF-κB signaling;
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学科分类号
摘要
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.
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页码:3050 / 3058
页数:8
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共 279 条
[1]  
Tysnes OB(2017)Epidemiology of Parkinson’s disease J Neural Transmission (Vienna, Austria 1996) 124 901-905
[2]  
Storstein A(2008)Parkinson’s disease: clinical features and diagnosis J Neurol Neurosurg Psychiatry 79 368-376
[3]  
Jankovic J(2011)Autonomic dysfunction in PD: a window to early detection? J Neurol Sci 310 118-122
[4]  
Goldstein DS(2015)Gastrointestinal autonomic dysfunction in patients with parkinson’s disease J Movement Disorders 8 76-82
[5]  
Sewell L(2016)Short chain fatty acids and gut microbiota differ between patients with Parkinson’s disease and age-matched controls Parkinsonism Relat Disord 32 66-72
[6]  
Sharabi Y(2015)Colonic bacterial composition in Parkinson’s disease Movement Disorders 30 1351-1360
[7]  
Kim JS(2016)Propagation of Aβ, tau and α-synuclein pathology between experimental models and human reality: prions, propagons and propaganda Acta Neuropathol 131 1-3
[8]  
Sung HY(2016)Gut microbiota regulate motor deficits and neuroinflammation in a model of parkinson’s disease Cell 167 1469-1480.e1412
[9]  
Unger MM(2014)Emergence of fecal microbiota transplantation as an approach to repair disrupted microbial gut ecology Immunol Letters 162 77-81
[10]  
Spiegel J(2016)Fecal microbiota transplantation and its usage in neuropsychiatric disorders Clin Psychopharmacol Neurosci 14 231-237