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

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.

凋亡相关基因bax与Th蛋白在帕金森病大鼠黑质和纹状体细胞中的表达

目的:利用动物模型探讨bax和Th蛋白表达与帕金森病(PD)的关系。方法:60只SD大鼠随机分为6组,即对照组及PD组(PD模型3d、7d、14d、21d、28d组)。PD组均通过脑立体定向注入6-羟基多巴胺,均在处死前腹腔注入阿朴吗啡,观察30min大鼠旋转的次数,连续至第4周每分钟大于7次者为成功的PD模型。对照组立体定向注入抗坏血酸生理盐水。处死后制作石蜡切片,用免疫组化法检测bax、Th蛋白的阳性细胞数。结果:PD组纹状体和黑质神经细胞存在细胞凋亡,与对照组差异存在显著性,且bax蛋白表达在PD组大鼠纹状体和黑质细胞中3d组为最高,其后很快下降,但显著高于对照组。而Th蛋白表达在大鼠纹状体和黑质细胞中对照组为最高,在PD组很快下降。结论:6-羟基多巴胺能诱发大鼠黑质细胞凋亡,bax作为前凋亡蛋白在启动和诱导黑质细胞凋亡方面起着关键性的作用。