Involvement of CRH Receptors in the Neuroprotective Action of R-Apomorphine in the Striatal 6-OHDA Rat Model  

作　　者：Mustafa Varcin Eduard Bentea Steven Roosens Yvette Michotte Sophie Sarre 

机构地区：[1]Department of Pharmaceutical Chemistry and Drug Analysis,Center for Neurosciences,Vrije Universiteit Brussel,Faculty of Medicine and Pharmacy,Brussels,Belgium [2]Belgian Pharmacists Association,Medicines Control Laboratory,Brussels,Belgium

出　　处：《Neuroscience & Medicine》2013年第4期299-318,共20页神经系统科学与医药（英文）

基　　金：financial support of the Institute for the promotion of Innovation by Science and Technology in Flanders(IWT)(IWT420);National Fund for Scientific Research(FWO-Vlaanderen)(G.0071.05)and of the Research Council of the Vrije Universiteit Brussel;research grant from the IWT(IWT420).

摘　　要：The dopamine D1-D2 receptor agonist, R-apomorphine, has been shown to be neuroprotective in different models of Parkinson’s disease. Different mechanisms of action for this effect have been proposed, but not verified in the striatal 6-hydroxydopamine rat model. In this study, the expression of a set of genes involved in 1) signaling, 2) growth and differentiation, 3) neuronal regeneration and survival, 4) apoptosis and 5) inflammation in the striatum was measured after a subchronic R-apomorphine treatment (10 mg/kg/day, subcutaneously, during 11 days) in the striatal 6-hydroxydopamine rat model. The expression of 84 genes was analysed by using the rat neurotrophins and receptors RT2 ProfilerTM PCR array. The neuroprotective effects of R-apomorphine in the striatal 6-hydroxydopamine model were confirmed by neurochemical and behavioural analysis. The expression data suggest the observed neuroprotection involved the alteration of the gene and the protein expression levels of the anti-inflammatory corticotropin releasing hormone receptor (CRHR) 1 and the pro-inflammatory CRHR2 receptor confirming its potential anti-inflammatory action.The dopamine D1-D2 receptor agonist, R-apomorphine, has been shown to be neuroprotective in different models of Parkinson’s disease. Different mechanisms of action for this effect have been proposed, but not verified in the striatal 6-hydroxydopamine rat model. In this study, the expression of a set of genes involved in 1) signaling, 2) growth and differentiation, 3) neuronal regeneration and survival, 4) apoptosis and 5) inflammation in the striatum was measured after a subchronic R-apomorphine treatment (10 mg/kg/day, subcutaneously, during 11 days) in the striatal 6-hydroxydopamine rat model. The expression of 84 genes was analysed by using the rat neurotrophins and receptors RT2 ProfilerTM PCR array. The neuroprotective effects of R-apomorphine in the striatal 6-hydroxydopamine model were confirmed by neurochemical and behavioural analysis. The expression data suggest the observed neuroprotection involved the alteration of the gene and the protein expression levels of the anti-inflammatory corticotropin releasing hormone receptor (CRHR) 1 and the pro-inflammatory CRHR2 receptor confirming its potential anti-inflammatory action.

关 键 词：APOMORPHINE Gene Expression Inflammation Neuroprotection Parkinson’s Disease Striatal 6-Hydroxydopamine Rat Model 

分 类 号：R73[医药卫生—肿瘤]