Immunolocalisation of 14-3-3 isoforms in normal and scrapie-infected murine brain

Immunolocalisation of 14-3-3 isoforms in normal and scrapie-infected murine brain
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DOI:
10.1016/s0306-4522(01)00492-4
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发表时间:
2002-01-01
期刊:
影响因子:
3.3
通讯作者:
Fraser, JR
Fraser, JR
中科院分区:
医学3区
文献类型:
--
作者:
Baxter, HC;Liu, WG;Fraser, JR

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脑脊液中14-3-3蛋白的出现是一些神经退行性疾病的特征,包括散发性的克雅氏病。尽管如此。14-3-3蛋白具有良好的物理化学特性,已知存在于神经细胞中,对各亚型的神经解剖学定位知之甚少。用14-3-3亚型特异性抗体检测了14-3-3亚型抗体在正常小鼠脑内的分布和ME7瘙痒病感染引起的神经变性过程中观察到的变化。在正常大脑中,有两种主要的免疫标记模式,即β、γ、eta和zeta亚型,它们呈现出相似的分布模式,通常是在解剖核团中标记神经元胞体,但个体亚型表现出差异,显示出位置上的细微差异。Tau亚型仅见于海马体和延髓。在中枢神经系统灰质中可见epsilon异构体。在瘙痒病感染的小鼠大脑中,在疾病过程中会发生严重的病理变化。14-3-3亚型在海马区和丘脑中的分布有显著差异。重要的是,在小脑顶核和下丘脑外侧核中,14-3-3 ETA亚型和Prion蛋白都存在于相同的神经症患者中。我们对成年小鼠脑中14-3-3亚型分布的研究清楚地表明,特定的14-3-3亚型具有不同的神经定位模式。事实上,在终末瘙痒病中枢神经系统中的异构体标记在一些大脑区域丢失,但在另一些区域增加,这表明在神经退化过程中这些蛋白质的处理可能比之前认识到的要复杂得多。(C)2002年IBRO。爱思唯尔科学有限公司出版。版权所有。
The appearance of 14-3-3 proteins in the cerebrospinal fluid is characteristic of some neurodegenerative conditions which include sporadic Creutzfeldt-Jakob disease. Although. 14-3-3 proteins are physiochemically well characterised and are known to be present in neuronal cells little is known of the neuroanatomical localisation of the individual isoforms. Using 14-3-3 isoform, specific antibodies we have examined the distribution of the isoforms in normal murine brain and the changes observed during neurodegeneration as a result of ME7 scrapie infection. In normal brain there are two major patterns of immunolabelling, The beta, gamma, eta and zeta isoforms which exhibit a similar distribution pattern showing labelling of neuronal cell bodies often in particular anatomical nuclei, However the individual isoforms exhibit variation revealing subtle differences in location. The tau isoform was found only in the hippocampus and medulla. and the epsilon isoform was found throughout grey matter of the CNS. In the scrapie-infected murine brain, where severe pathological changes occur during the course of the disease. significant differences in the 14-3-3 isoform distribution were observed in the hippocampus and in the thalamus. Importantly, both the 14-3-3 eta isoform and prion protein were seen in the same neurotics in both the cerebellar roof nuclei and in the lateral hypothalamic nuclei.Our study of 14-3-3 isoform distribution in adult murine brain clearly demonstrates a heterogeneous pattern of neurolocation for specific 14-3-3 isoforms. The fact that isoform labelling in terminal scrapie CNS is lost in some brain areas, but increases in others, suggests that the processing of these proteins during neurodegeneration may be much more complex than previously recognised. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved.