Efflux mechanisms at the developing brain barriers: ABC-transporters in the fetal and postnatal rat
Efflux mechanisms at the developing brain barriers: ABC-transporters in the fetal and postnatal rat
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DOI：
10.1016/j.toxlet.2010.04.025
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发表时间：
2010-08-01
影响因子：
3.5
通讯作者：
Saunders, Norman R.
中科院分区：
文献类型：
--
作者：
Ek, C. Joakim;Wong, Annamae;Saunders, Norman R.
存在于血脑屏障界面处的ATP结合盒（ABC）家族的蛋白质已显示通过主动外排减少化合物从血液进入脑。它们的底物多种多样，包括许多药物和毒素，因此为脑神经保护提供了重要机制。然而，关于它们在发育中的大脑中的存在和功能的知识非常有限。我们使用qPCR和免疫细胞化学来确定胎儿和新生大鼠脑血管（血脑屏障部位）和脉络丛（血-CSF屏障部位）中四种主要屏障ABC转运蛋白（pgp/ABCB 1、MRP 1/ABCC 1、MRP 4/ABCC 4和BCRP/ABCG 2）的基因表达和定位。该研究表明，ABC转运蛋白即使在早期胎儿阶段也定位于脑屏障，尽管胎儿中的pgp表达较低，但其他转运蛋白在胎儿和成人脑中的表达水平相当，这表明除了胎盘提供的保护外，还对脑有直接的神经保护作用。BCRP在发育中的脉络丛中表达水平较高，仅在胎儿期在上皮细胞的血液面侧检测到，表明该转运蛋白对早期脑外排机制具有特殊作用。(C)2010爱思唯尔爱尔兰有限公司版权所有。
Proteins of the ATP-binding cassette (ABC) family, present at the blood-brain barrier interfaces, have been shown to reduce the entry of compounds from blood into the brain by active efflux. Their substrates are diverse including many drugs and toxins and therefore provide an important mechanism for brain neuroprotection. However, knowledge of their presence and function in the developing brain is very limited. We have used qPCR and immunocytochemistry to determine gene expression and localisation of four main barrier ABC-transporters (pgp/ABCB1, MRP1/ABCC1, MRP4/ABCC4 and BCRP/ABCG2) in the fetal and neonatal rat brain cerebral blood vessels (site of blood-brain barrier) and choroid plexus (site of blood-CSF barrier). The study shows that ABC-transporters localise to the brain barriers even at early fetal stages and although pgp expression was lower in the fetus, the other transporters were expressed at comparable levels in fetal and adult brains suggesting direct neuroprotection of the brain in addition to that provided by the placenta. BCRP was expressed at higher levels in developing choroid plexus and was only detected at fetal stages on the blood-facing side of epithelial cells indicating a particular role of this transporter for early brain efflux mechanisms. (C) 2010 Elsevier Ireland Ltd. All rights reserved.