Ulcerative colitis exacerbates lipopolysaccharide-induced damage to the nigral dopaminergic system: potential risk factor in Parkinson's disease
Ulcerative colitis exacerbates lipopolysaccharide-induced damage to the nigral dopaminergic system: potential risk factor in Parkinson's disease
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DOI：
10.1111/j.1471-4159.2010.06879.x
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发表时间：
2010-09-01
影响因子：
4.7
通讯作者：
Machado, Alberto
中科院分区：
文献类型：
--
作者：
Villaran, Ruth F.;Espinosa-Oliva, Ana M.;Machado, Alberto
外周炎症在某些神经退行性疾病的发生和发展中起作用。为了确定这种可能性，多巴胺能神经变性的基础上注射的炎症剂脂多糖（LPS）的黑质内的模型进行了测定，在大鼠溃疡性结肠炎（UC）的摄入葡聚糖硫酸钠诱导。我们发现血清中的炎症标志物水平增加（肿瘤坏死因子-α、IL-1 β、IL-6和急性期蛋白C-反应蛋白）和黑质（肿瘤坏死因子-α、IL-1 β、IL-6、诱导型一氧化氮合酶、细胞间粘附分子-1、小胶质细胞和星形胶质细胞群），以及血脑屏障通透性的改变和多巴胺能神经元的损失。UC加强了LPS的炎症和有害作用。相反，包封在脂质体中的氯膦酸盐（ClodLip），其消耗外周巨噬细胞，改善LPS和UC的作用。外周炎症可能是帕金森病发展的一个危险因素。
Peripheral inflammation could play a role in the origin and development of certain neurodegenerative disorders. To ascertain this possibility, a model of dopaminergic neurodegeneration based on the injection of the inflammatory agent lipopolysaccharide (LPS) within the substantia nigra was assayed in rats with ulcerative colitis (UC) induced by the ingestion of dextran sulphate sodium. We found an increase in the levels of inflammatory markers from serum (tumor necrosis factor-alpha, IL-1 beta, IL-6 and the acute phase protein C-reactive protein) and substantia nigra (tumor necrosis factor-alpha, IL-1 beta, IL-6, inducible nitric oxide synthase, intercellular adhesion molecule-1, microglial and astroglial populations) of rats with UC, as well as an alteration of the blood-brain barrier permeability and the loss of dopaminergic neurons. UC reinforced the inflammatory and deleterious effects of LPS. On the contrary, clodronate encapsulated in liposomes (ClodLip), which depletes peripheral macrophages, ameliorated the effect of LPS and UC. Peripheral inflammation might represent a risk factor in the development of Parkinson's disease.