Osteopontin expression in substantia nigra in MPTP-treated primates and in Parkinson's disease
Osteopontin expression in substantia nigra in MPTP-treated primates and in Parkinson's disease
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DOI：
10.1016/j.brainres.2006.08.036
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发表时间：
2006-11-06
期刊：
影响因子：
2.9
通讯作者：
Jenner, Peter
中科院分区：
文献类型：
--
作者：
Iczkiewicz, Joanna;Jackson, Michael J.;Jenner, Peter
帕金森病(PD)是以黑质(SN)多巴胺能神经元缺失为特征的疾病，其发病机制尚不清楚。细胞死亡涉及氧化应激和炎症机制，而这些机制可以通过糖基化的磷蛋白骨桥蛋白(OPN)的作用而改变。OPN存在于大鼠黑质中，但其在人类和非人类灵长类动物脑中的存在尚未得到广泛研究。正常绒猴SN中存在OPN mRNA和蛋白，OPN蛋白定位于黑质神经元，尽管这些神经元不是多巴胺能细胞，也不存在于神经胶质细胞。相反，在正常人SN的多巴胺能神经元中发现了OPN蛋白，但在神经胶质细胞中也没有发现OPN蛋白，并在细胞外基质中积累了一些。经MPTP处理后，OPN蛋白的表达降低，但其mRNA水平没有变化，激活的小胶质细胞和星形胶质细胞中都不存在OPN蛋白。在PD的SN中，OPN蛋白在剩余的多巴胺能神经元中表达减少，在激活的小胶质细胞中表达，而在星形胶质细胞中不表达。这不是PD所特有的，因为在多系统萎缩和进行性核上性麻痹中，OPN蛋白在SN中的表达也减少，而且该蛋白的定位相同。OPN在正常人和非人灵长类SN中的存在，加上其在黑质细胞变性后表达的减少，表明它可能在多巴胺能神经元的存活中发挥重要作用。(C)2006爱思唯尔B.V.保留所有权利。
Parkinson's disease (PD) is characterised by the loss of dopaminergic neurones in the substantia nigra (SN) but the pathogenic mechanism remains unknown. Cell death involves oxidative stress and inflammatory mechanisms, and these may be altered by the actions of the glycosylated phosphoprotein osteopontin (OPN). OPN is present in the rat SN, but its presence in human and non-human primate brain has not been extensively studied. Both OPN mRNA and protein were present in the normal marmoset SN, and OPN protein was localised to nigral neurones although these were not dopaminergic cells and it was not present in glial cells. In contrast, OPN protein was found in dopaminergic neurones in the normal human SN but again not in glial cells with some accumulation in the extracellular matrix. Following MPTP treatment of common marmosets, OPN protein expression was decreased, although its mRNA levels were unchanged and it was not present in either activated microglia or astrocytes. In the SN in PD, OPN protein expression was decreased in the remaining dopaminergic neurones and it was present in activated microglia but not in astrocytes. This was not specific to PD as OPN protein expression was also decreased in the SN in multiple system atrophy and progressive supranuclear palsy with an identical localisation of the protein. The presence of OPN in the normal human and non-human primate SN coupled to its decreased expression following nigral cell degeneration suggests that it may play an important role in dopaminergic neurone survival. (c) 2006 Elsevier B.V. All rights reserved.