Gut microbiota dysbiosis contributes toα-synuclein-related pathology associated with C/EBPβ/AEP signaling activation in a mouse model of Parkinson’s disease  

作　　者：Xiaoli Fang Sha Liu Bilal Muhammad Mingxuan Zheng Xing Ge Yan Xu Shu Kan Yang Zhang Yinghua Yu Kuiyang Zheng Deqin Geng Chun-Feng Liu 

机构地区：[1]Department of Neurology and Clinical Research Center of Neurological Disease,The Second Affiliated Hospital of Soochow University,Suzhou,Jiangsu Province,China [2]Department of Neurology,Affiliated Hospital of Xuzhou Medical University,Xuzhou,Jiangsu Province,China [3]Jiangsu Key Laboratory of Immunity and Metabolism,Department of Pathogen Biology and Immunology,Xuzhou Medical University,Xuzhou,Jiangsu Province,China [4]Department of Neurology,Xuzhou Central Hospital,Xuzhou,Jiangsu Province,China [5]Jiangsu Key Laboratory of Neuropsychiatric Disease and Institute of Neuroscience,Soochow University,Suzhou,Jiangsu Province,China

出　　处：《Neural Regeneration Research》2024年第9期2081-2088,共8页中国神经再生研究（英文版）

基　　金：supported by Jiangsu Provincial Medical Key Discipline,No.ZDXK202217(to CFL);Jiangsu Planned Projects for Postdoctoral Research Funds,No.1601056C(to SL).

摘　　要：Parkinson’s disease is a neurodegenerative disease characterized by motor and gastrointestinal dysfunction.Gastrointestinal dysfunction can precede the onset of motor symptoms by several years.Gut microbiota dysbiosis is involved in the pathogenesis of Parkinson’s disease,whether it plays a causal role in motor dysfunction,and the mechanism underlying this potential effect,remain unknown.CCAAT/enhancer binding proteinβ/asparagine endopeptidase(C/EBPβ/AEP)signaling,activated by bacterial endotoxin,can promoteα-synuclein transcription,thereby contributing to Parkinson’s disease pathology.In this study,we aimed to investigate the role of the gut microbiota in C/EBPβ/AEP signaling,α-synuclein-related pathology,and motor symptoms using a rotenone-induced mouse model of Parkinson’s disease combined with antibiotic-induced microbiome depletion and fecal microbiota transplantation.We found that rotenone administration resulted in gut microbiota dysbiosis and perturbation of the intestinal barrier,as well as activation of the C/EBP/AEP pathway,α-synuclein aggregation,and tyrosine hydroxylase-positive neuron loss in the substantia nigra in mice with motor deficits.However,treatment with rotenone did not have any of these adverse effects in mice whose gut microbiota was depleted by pretreatment with antibiotics.Importantly,we found that transplanting gut microbiota derived from mice treated with rotenone induced motor deficits,intestinal inflammation,and endotoxemia.Transplantation of fecal microbiota from healthy control mice alleviated rotenone-induced motor deficits,intestinal inflammation,endotoxemia,and intestinal barrier impairment.These results highlight the vital role that gut microbiota dysbiosis plays in inducing motor deficits,C/EBPβ/AEP signaling activation,andα-synuclein-related pathology in a rotenone-induced mouse model of Parkinson’s disease.Additionally,our findings suggest that supplementing with healthy microbiota may be a safe and effective treatment that could help ameliorate the progr

关 键 词：C/EBP/AEP signaling pathway ENDOTOXEMIA fecal microbiota transplantation intestinal barrier intestinal inflammation microbiota-gut-brain axis Parkinson’s disease 

分 类 号：R742.5[医药卫生—神经病学与精神病学] R-332[医药卫生—临床医学]