MPTP公司
非诺贝特
贝扎纤维
内分泌学
药理学
内科学
多巴胺能
阿扑吗啡
化学
医学
兴奋剂
神经保护
多巴胺
受体
作者
Alexandre Kreisler,Alain Duhamel,Christel Vanbesien-Mailliot,Alain Destée,Régis Bordet
出处
期刊:Behavioural Pharmacology
[Ovid Technologies (Wolters Kluwer)]
日期:2010-05-01
卷期号:21 (3): 194-205
被引量:18
标识
DOI:10.1097/fbp.0b013e32833a5c81
摘要
Earlier study from our group indicated that the peroxisome proliferator-activated receptor-alpha agonist fenofibrate prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic cell loss in C57Bl/6 mice. Our objective was to determine whether or not fibratescan improve motor activity in two experimental models of Parkinson's disease: the MPTP C57Bl/6 mouse and the 6-hydroxydopamine (6-OHDA) Wistar rat. Six groups of mice were set up: sham, sham-fenofibrate, sham-bezafibrate, MPTP, MPTP-fenofibrate and MPTP-bezafibrate. Mice were fed a diet containing 0.2% fenofibrate, 0.2% bezafibrate or no hypolipidaemic agent for 2 weeks. Four groups of rats were set up: sham, sham-fenofibrate, 6-OHDA and 6-OHDA-fenofibrate. Rats were fed a diet containing 0.2% fenofibrate or no hypolipidaemic agent for 4 weeks. In mice, motor activity was quantified using actimetry. Nine parameters were recorded. The results were analyzed with a mixed linear model. In rats, behavioural sensitization was studied with repetitive injections of apomorphine. All the actimetry parameters indicated a decrease of locomotion the day after MPTP injections and eight parameters improved in MPTP mice treated with fenofibrate or bezafibrate. The apomorphine-induced rotation behaviour mildly decreased in 6-OHDA rats treated with fenofibrate, but behavioural sensitization was unchanged. The 6-OHDA and MPTP compounds have different toxicity mechanisms, which could explain why we did not observe the same effect in 6-OHDA rats as in MPTP mice. These data suggest that the protective effect of fibrates can be carried through inhibition of inflammation rather than oxidative stress.
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