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Twice subacute MPTP administrations induced time-dependent dopaminergic neurodegeneration and inflammation in midbrain and ileum, as well as gut microbiota disorders in PD mice.
NeuroToxicology ( IF 3.4 ) Pub Date : 2019-11-29 , DOI: 10.1016/j.neuro.2019.11.009
Wenjun Xie 1 , Jieying Gao 1 , Rong Jiang 2 , Xinrong Liu 1 , Feng Lai 3 , Yong Tang 4 , Hong Xiao 1 , Yan Jia 1 , Qunhua Bai 1
Affiliation  

Parkinson's disease (PD) is a common progressive neurodegenerative disease. PD produces a pathological state in the intestine and disordered gut microbiota (GM), which may be important for the pathogenesis and progression of PD, but it is not clear. To explore the conditions and characteristics of intestinal pathology and GM disorders when PD-related injuries occur, we used twice 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) subacute administration with an interval of 3 weeks (each was an intraperitoneal injection of 25 mg/kg MPTP for 5 consecutive days). We observed the changes in intestinal and brain immune status, intestinal barrier function and GM in different injury states one day, one week, and three weeks after the first stimulus and one day and one week after the second stimulus. Our study found that two subacute administrations of MPTP induced dopaminergic (DAergic) neuron injury and inflammation in the midbrain and ileum, impaired intestinal barrier function and GM disorders closely related to administration. These changes recovered after the first administration, but after repeated administration, some indicators showed more dramatic changes than during the first administration. Our results suggest that the intestinal tract is sensitive to PD-related injury, and the GM is susceptible to disturbances caused by intestinal function, which may be concerned in local immune disorders of the intestine.

中文翻译:

两次亚急性MPTP给药会引起中脑和回肠的时间依赖性多巴胺能神经退行性变和炎症,以及PD小鼠的肠道菌群失调。

帕金森氏病(PD)是一种常见的进行性神经退行性疾病。PD在肠道和肠道菌群失调(GM)中产生病理状态,这可能对PD的发病机理和进展很重要,但目前尚不清楚。为了探讨PD相关损伤发生时肠道病理学和GM疾病的状况和特征,我们使用两次1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)亚急性给药两次,间隔3周(每次都是连续5天腹膜内注射25 mg / kg MPTP)。我们观察到在第一次刺激后的一天,一周和三周以及第二次刺激后的一天和一周,不同损伤状态下肠道和大脑免疫状态,肠屏障功能和GM的变化。我们的研究发现,两次MPTP亚急性给药引起中脑和回肠多巴胺能(DAergic)神经元损伤和炎症,肠屏障功能受损和GM紊乱与给药密切相关。这些变化在第一次给药后得以恢复,但是在重复给药后,一些指标显示出比第一次给药更显着的变化。我们的结果表明,肠道对PD相关损伤敏感,而GM对肠道功能引起的紊乱敏感,这可能与肠道局部免疫功能紊乱有关。这些变化在第一次给药后得以恢复,但是在重复给药后,一些指标显示出比第一次给药更显着的变化。我们的结果表明,肠道对PD相关损伤敏感,而GM对肠道功能引起的紊乱敏感,这可能与肠道局部免疫功能紊乱有关。这些变化在第一次给药后得以恢复,但是在重复给药后,一些指标显示出比第一次给药更显着的变化。我们的结果表明,肠道对PD相关损伤敏感,而GM对肠道功能引起的紊乱敏感,这可能与肠道局部免疫功能紊乱有关。
更新日期:2019-11-29
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