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作 者:Hairong Peng Shui Yu Yukai Zhang Yanqing Yin Jiawei Zhou
机构地区:[1]Institute of Neuroscience,State Key Laboratory of Neuroscience,CAS Center for Excellence in Brain Science and Intelligence Technology,Chinese Academy of Sciences,Shanghai,200031,China [2]School of Future Technology,University of Chinese Academy of Sciences,Beijing,100049,China [3]Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology,Shanghai,201210,China
出 处:《Neuroscience Bulletin》2022年第8期871-886,共16页神经科学通报(英文版)
基 金:This work was supported by grants from the Ministry of Science and Technology of China(2020YFC2002800);the Natural Science Foundation of China(U1801681);Strategic Priority Research Program of Chinese Academy of Science(XDB32020100);Shanghai Municipal Science and Technology Major Project(2018SHZDZX05);Key Realm R&D Program of Guangdong Province(2018B030337001);Innovative Research Team of High-Level Local Universities in Shanghai.
摘 要:A wealth of evidence has suggested that gastrointestinal dysfunction is associated with the onset and progression of Parkinson’s disease(PD).However,the mechanisms underlying these links remain to be defined.Here,we investigated the impact of deregulation of intestinal dopamine D2 receptor(DRD2)signaling in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced dopaminergic neurodegeneration.Dopamine/dopamine signaling in the mouse colon decreased with ageing.Selective ablation of Drd2,but not Drd4,in the intestinal epithelium,caused a more severe loss of dopaminergic neurons in the substantia nigra following MPTP challenge,and this was accompanied by a reduced abundance of succinate-producing Alleoprevotella in the gut microbiota.Administration of succinate markedly attenuated dopaminergic neuronal loss in MPTP-treated mice by elevating the mitochondrial membrane potential.This study suggests that intestinal epithelial DRD2 activity and succinate from the gut microbiome contribute to the maintenance of nigral DA neuron survival.These findings provide a potential strategy targeting neuroinflammation-related neurological disorders such as PD.
关 键 词:INTESTINE DRD2 Parkinson’s disease MPTP SUCCINATE Mitochondria
分 类 号:R338[医药卫生—人体生理学]
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