Apolipoprotein E expression by neurons surviving excitotoxic stress
Apolipoprotein E expression by neurons surviving excitotoxic stress
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DOI：
10.1006/nbdi.1999.0251
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发表时间：
1999-12-01
影响因子：
6.1
通讯作者：
Catsicas, S
中科院分区：
文献类型：
--
作者：
Boschert, U;Merlo-Pich, E;Catsicas, S
在成人脑中，载脂蛋白E（apoE）mRNA被认为由非神经元细胞表达。然而，当脑损伤发生时，这种蛋白质存在于神经元中。我们已经研究了载脂蛋白E的表达后，全身红藻氨酸（KA），注射在大鼠海马神经退行性变。我们描述了两种效果。首先，星形胶质细胞中apoE水平的适度增加。第二，出乎意料的是，在CA 1和CA 3锥体神经元簇中apoE mRNA水平非常强烈的增加。这些细胞的神经元身份得到了一系列观察结果的支持。首先，在具有锥体神经元形态特征的细胞中发现apoE杂交信号。第二，细胞对神经元标记物MAP 2呈阳性。第三，细胞对星形胶质细胞标记物GFAP和小胶质细胞标记物0X 42呈阴性。第四，与c-fos杂交的探针发现了相同的分布模式，c-fos是一种在应激下在神经元中瞬时表达的转录因子。在KA后48和72 h，大部分兴奋性毒性细胞死亡已经发生。由于apoE阳性锥体神经元中没有观察到程序性细胞死亡的形态学迹象，我们认为apoE表达的神经元可能是一个救援计划的一部分，以抵消神经变性。(C)北京：科学出版社.
In the adult brain, apolipoprotein E (apoE) mRNA is thought to be expressed by nonneuronal cells. Yet, when a brain damage has occurred, the protein is found in neurons. We have studied apoE expression following systemic kainic acid (KA), injected in rats to induce hippocampal neurodegeneration. We describe two effects. First, a moderate increase of apoE levels in astrocytes. Second, and unexpected, a very strong increase of apoE mRNA levels in clusters of CA1 and CA3 pyramidal neurons. Neuronal identity of these cells is supported by a series of observations. First, apoE hybridization signals were found in cells with morphological characteristics of pyramidal neurons. Second, the cells were positive for the neuronal marker MAP2. Third, the cells were negative for the astrocytic marker GFAP and for the microglia marker OX42. Fourth, the same distribution pattern was found with probes hybridizing to c-fos, a transcription factor transiently expressed in neurons under stress. At 48 and 72 h following KA, most of the excitotoxic cell death had already occurred. Since no morphological signs of programmed cell death were observed in apoE-positive pyramidal neurons, we suggest that expression of apoE by neurons may be part of a rescue program to counteract neurodegeneration. (C) 1999 Academic Press.