Kawamoto Yasuhiro, Akiguchi Ichiro, Jarius Christa, Budka Herbert
Department of Neurology, Faculty of Medicine, Kyoto University, 54 Shogoin-Kawaharacho, Sakyoku, 606-8507 Kyoto, Japan.
Acta Neuropathol. 2004 Oct;108(4):302-8. doi: 10.1007/s00401-004-0892-5. Epub 2004 Jul 3.
14-3-3 proteins have been reported to be detected specifically in the cerebrospinal fluid (CSF) from patients with Creutzfeldt-Jakob disease (CJD). To elucidate the role of 14-3-3 proteins in patients with CJD, we performed immunohistochemical studies on 14-3-3 proteins in autopsied brains from five patients with sporadic CJD (sCJD), three patients with Alzheimer's disease (AD), and seven normal control subjects. Formalin-fixed, paraffin-embedded sections from all cases were immunostained with several types of specific anti-14-3-3 antibodies. In the normal control brains, 14-3-3 immunoreactivity was localized mainly in the neuronal somata and processes; in contrast, glial cells showed no or faint immunoreactivity. In the brains from the patients with AD, 14-3-3 immunoreactivity was observed in the surviving neurons as well as some neurofibrillary tangles. In the brains from the patients with sCJD, 14-3-3 immunoreactivity was well preserved in the remaining neurons. Furthermore, the glial cells, especially the reactive astrocytes, were intensely immunostained in the brains affected by sCJD. Our findings suggest that 14-3-3 proteins may be up-regulated in the glial cells, particularly in reactive astrocytes, and that the enhanced expression of 14-3-3 proteins in these glial elements may be associated with the pathogenesis of sCJD.
据报道,在克雅氏病(CJD)患者的脑脊液(CSF)中可特异性检测到14-3-3蛋白。为阐明14-3-3蛋白在CJD患者中的作用,我们对5例散发性CJD(sCJD)患者、3例阿尔茨海默病(AD)患者及7名正常对照者尸检大脑中的14-3-3蛋白进行了免疫组化研究。所有病例的福尔马林固定、石蜡包埋切片均用几种特异性抗14-3-3抗体进行免疫染色。在正常对照大脑中,14-3-3免疫反应主要定位于神经元胞体和突起;相比之下,胶质细胞无免疫反应或免疫反应微弱。在AD患者的大脑中,在存活的神经元以及一些神经原纤维缠结中观察到14-3-3免疫反应。在sCJD患者的大脑中,14-3-3免疫反应在剩余的神经元中保存良好。此外,在受sCJD影响的大脑中,胶质细胞,尤其是反应性星形胶质细胞,被强烈免疫染色。我们的研究结果表明,14-3-3蛋白可能在胶质细胞中上调,尤其是在反应性星形胶质细胞中,并且这些胶质细胞成分中14-3-3蛋白的表达增强可能与sCJD的发病机制有关。