Localization of mRNA expression of P-glycoprotein at the blood-brain barrier and in the hippocampus
Localization of mRNA expression of P-glycoprotein at the blood-brain barrier and in the hippocampus
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DOI：
10.1196/annals.1314.048
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发表时间：
2004-01-01
期刊：
影响因子：
--
通讯作者：
De Kloet, ER
中科院分区：
文献类型：
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作者：
Karssen, AM;Meijer, OC;De Kloet, ER
多药耐药(MDR)P-糖蛋白是一种能量依赖的外排转运蛋白，可以保护大脑免受各种神经毒性化合物的伤害。这种跨膜蛋白是血脑屏障的一个众所周知的功能成分，也可能存在于其他脑细胞中。我们已经开发了一种针对小鼠mdr1基因的核探针，可以识别啮齿动物mdr1基因的两种异构体，以确定P-糖蛋白表达的准确定位。我们还研究了一种已知的P-糖蛋白表达诱导剂的治疗效果。Mdr1基因原位杂交结果表明，mdr1基因表达于大鼠全脑毛细血管内皮细胞，提示P-糖蛋白表达于构成血脑屏障的内皮细胞。令人惊讶的是，在海马区的神经元层，特别是在齿状回的颗粒细胞中，也发现了mdr1基因的特异性表达。红藻氨酸处理后6h和24h，齿状回mdr1mRNA的表达水平降低。我们的数据表明P-糖蛋白在内皮细胞和可能的齿状回神经元中表达，但P-糖蛋白在齿状回神经元中的功能作用目前尚不清楚。
The multidrug resistance (mdr) P-glycoprotein is an energy-dependent efflux transporter that protects the brain against a wide variety of neurotoxic compounds. This transmembrane protein is a well-known functional component of the blood-brain barrier and might be present in other brain cells as well. We have developed a riboprobe against the murine mdr1 mRNA recognizing both isoforms of the rodent mdr1 gene to determine the exact localization of P-glycoprotein expression. We have also studied the effects of treatment with a known inducer of P-glycoprotein expression. In situ mRNA hybridization demonstrates that mdr1 mRNA is present in the endothelial cells of brain capillaries throughout the rat brain, indicating that P-glycoprotein is expressed at the endothelial cells forming the blood-brain barrier. Surprisingly, specific mdr1 mRNA expression was also found in neuronal layers of hippocampal fields, particularly in the granule cells of the dentate gyrus. Kainic acid treatment decreased the expression levels of mdr1 mRNA in the dentate gyrus 6 and 24 h after treatment. Our data indicate that P-glycoprotein is expressed by endothelial cells and possibly dentate gyrus neurons The functional role of P-glycoprotein at dentate gyrus neurons is presently unknown.