DEVELOPMENTAL EXPRESSION OF THE PRION PROTEIN GENE IN GLIAL-CELLS
DEVELOPMENTAL EXPRESSION OF THE PRION PROTEIN GENE IN GLIAL-CELLS
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DOI：
10.1016/0896-6273(95)90307-0
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发表时间：
1995-03-01
期刊：
影响因子：
16.2
通讯作者：
OESCH, B
中科院分区：
文献类型：
--
作者：
MOSER, M;COLELLO, RJ;OESCH, B
朊病毒的复制依赖于宿主蛋白 PrPc 的存在。在疾病过程中，PrPc 转化为异常亚型 PrPSc，并在大脑中积聚。鉴定发生朊病毒复制和 PrP 转化的细胞类型的尝试已得出相互矛盾的结果。尽管 PrP mRNA 在动物的整个生命周期中神经元中大量存在，但 PrPSc 最初在星形胶质细胞和可能的其他神经胶质细胞中积聚，并在疾病后期在组织中广泛扩散，通常在白质中。我们在此报道，PrP mRNA 不仅在神经元中表达，而且在出生后仓鼠和大鼠整个大脑的星形胶质细胞和少突胶质细胞中表达。新生动物中胶质 PrP mRNA 表达水平与神经元相当，并且在出生后发育过程中增加两倍。因此，排出 PrP mRNA 的很大一部分是由神经胶质细胞贡献的。我们的结果为白质组织和神经胶质细胞的细胞质中 PrPSc 的积累提供了解释，并论证了神经胶质细胞直接参与朊病毒传播。
Replication of prions is dependent on the presence of the host protein PrPc. During the course of disease, PrPc is converted into an abnormal isoform, PrPSc, which accumulates in the brain. Attempts to identify the cell type(s) in which prion replication and PrP conversion occur have reached conflicting results. Although PrP mRNA is present in high amounts in neurons throughout the life of the animal, PrPSc initially accumulates in astrocytes and possibly other glial cells and, later in the course of the disease, spreads diffusely in the tissue, often in white matter. We report here that PrP mRNA is expressed not only in neurons but also in astrocytes and oligodendrocytes throughout the brain of postnatal hamsters and rats. The level of glial PrP mRNA expression in neonatal animals was comparable to that of neurons and increased two-fold during postnatal development. A substantial portion of drain PrP mRNA is therefore contributed by glial cells. Our results provide an explanation for the accumulation of PrPSc in white matter tissue and in the cytoplasm of glial cells and argue for a direct involvement of glia in prion propagation.