Glial fibrillary acidic protein is necessary for mature astrocytes to react to β‐amyloid
Glial fibrillary acidic protein is necessary for mature astrocytes to react to β‐amyloid
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胶质纤维酸性蛋白是成熟星形胶质细胞对β淀粉样蛋白反应所必需的
DOI：
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发表时间：
1999
期刊：
影响因子：
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通讯作者：
J. Silver
中科院分区：
文献类型：
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作者：
Kexing Xu;A. Malouf;A. Messing;J. Silver
星形胶质细胞中胶质纤维酸性蛋白(GFAP)的上调是反应性胶质增生症的一个特征，然而，GFAP在这一过程中的功能在很大程度上是未知的。我们以前的研究表明，成熟星形胶质细胞通过多种方式对底物结合的β-淀粉样蛋白(BAP)做出强烈反应(即增加胶质纤维酸性蛋白，增强运动性，异常聚集模式，抑制细胞外基质产生)。为了揭示这些现象中的哪些与GFAP的功能有因果关系，将缺乏GFAP的转基因小鼠的原代星形胶质细胞以低密度或高密度培养在BAP底物上，并在体外成熟后进行不同时间的培养。当细胞在体外成熟两周或更长时间，特别是在高密度培养时，突变细胞和对照细胞之间的差异变得越来越明显。成熟的对照星形胶质细胞对BAP表现出戏剧性的反应，聚集成绳状结构的网络，完全桥接在多肽表面。与之形成鲜明对比的是，GFAP缺失的成熟星形胶质细胞启动反应的速度要慢得多，紧密聚集的能力也大大降低。此外，我们制备了GFAP−/−和GFAP+/+小鼠的海马片培养物，并比较了它们对注射BAP的星形胶质细胞的反应。海马片培养的−/−星形胶质细胞与GFAP+/+星形胶质细胞一样，未能在沉积边缘形成屏障样结构。我们的数据表明，GFAP可能是成熟星形胶质细胞抑制大脑中某些类型的高度炎症性病变所必需的。Glia 25：390-403,1999。©1999 Wiley-Liss，Inc.
Upregulation of the glial fibrillary acidic protein (GFAP) in astrocytes is a hallmark of the phenomenon known as reactive gliosis and, yet, the function of GFAP in this process is largely unknown. Our previous studies have shown that mature astrocytes react vigorously to substrate bound β‐amyloid protein (BAP) in a variety of ways (i.e., increased GFAP, enhanced motility, unusual aggregation patterns, inhibitory ECM production). In order to uncover which, if any, of these phenomena are causally related to the function of GFAP, primary cortical astrocytes from transgenic mice lacking GFAP were cultured on BAP substrates at low or high density and at various lengths of time following in vitro maturation. Differences between mutant and control cells became progressively more obvious when cells were matured in vitro for two weeks or longer and especially in cultures that were at high density. Mature control astrocytes show a dramatic response to BAP by aggregating into a meshwork of rope‐like structures that completely bridge over the peptide surface. In marked contrast, mature GFAP‐null astrocytes initiate the response much more slowly and had a much reduced ability to aggregate tightly. Furthermore, we prepared hippocampal slice cultures from GFAP−/− and GFAP+/+ mice and compared their astrocytic responses to injected BAP. GFAP−/− astrocytes of hippocampal slice cultures failed to form a barrier‐like structure around the edge of the BAP deposit as did GFAP+/+ astrocytes. Our data suggest that GFAP may be essential for mature astrocytes to constrain certain types of highly inflammatory lesions in the brain. GLIA 25:390–403, 1999. © 1999 Wiley‐Liss, Inc.
影响因子：
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作者：
Lawrence F. Eng;Albert C.H. Yu;Yuen‐Ling Lee
通讯作者：
Lawrence F. Eng;Albert C.H. Yu;Yuen‐Ling Lee