Enhanced expression of 14-3-3 proteins in reactive astrocytes in Creutzfeldt-Jakob disease brains

Enhanced expression of 14-3-3 proteins in reactive astrocytes in Creutzfeldt-Jakob disease brains
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DOI:
10.1007/s00401-004-0892-5
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发表时间:
2004-10-01
影响因子:
12.7
通讯作者:
Budka, H
Budka, H
中科院分区:
医学1区
文献类型:
--
作者:
Kawamoto, Y;Akiguchi, I;Budka, H

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14-3-3蛋白已被报道在克雅氏病(Creutzfeldt-Jakob disease,CJD)患者的脑脊液(cerebralfluid,CSF)中特异性检测到。为了阐明14-3-3蛋白在CJD患者中的作用,我们对5名散发性CJD(sCJD)患者,3名阿尔茨海默病(AD)患者和7名正常对照者的尸检脑组织中的14-3-3蛋白进行了免疫组织化学研究。福尔马林固定,石蜡包埋切片从所有的情况下,免疫染色与几种类型的特异性抗14-3-3抗体。在正常对照组脑中,14-3-3免疫反应主要定位于神经元胞体和突起;相反,胶质细胞显示无或微弱的免疫反应。在AD患者的脑中,在存活的神经元以及一些神经元缠结中观察到14-3-3免疫反应性。在sCJD患者的大脑中,14-3-3免疫反应性在剩余的神经元中保存良好。此外,胶质细胞,特别是反应性星形胶质细胞,在sCJD患者的大脑中强烈的免疫染色。我们的研究结果表明,14-3-3蛋白可能是上调的胶质细胞,特别是在反应性星形胶质细胞,和14-3-3蛋白在这些胶质细胞元素的表达增强可能与sCJD的发病机制。
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.