Vascular and extravascular distribution of the ATP-binding cassette transporters ABCB1 and ABCC1 in aged human brain and pituitary
Vascular and extravascular distribution of the ATP-binding cassette transporters ABCB1 and ABCC1 in aged human brain and pituitary
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DOI：
10.1016/j.mad.2014.08.003
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发表时间：
2014-11-01
影响因子：
5.3
通讯作者：
Pahnke, Jens
中科院分区：
文献类型：
--
作者：
Bernstein, Hans-Gert;Hoelzl, Gloria;Pahnke, Jens
ATP结合盒（ABC）转运蛋白在理解神经退行性疾病（ND）（如阿尔茨海默病和帕金森病）中的病理性肽沉积方面发挥着越来越重要的作用。为了描述NDs在人脑组织中最重要的ABC转运蛋白的位置，我们研究了ABCB 1和ABCC 1在成年人脑和垂体中的免疫组织学。两种转运蛋白具有相似但不相同的表达模式。在具有已建立的血脑屏障（BBB）的脑区域中，ABCB 1和ABCC 1在微血管的内皮细胞和较大血管的子集（主要是小静脉）中普遍表达。值得注意的是，这两种转运蛋白也被发现在脑室周围器官中的有孔毛细血管中，其中BBB是不存在的。此外，ABCB 1和ABCC 1还表达于各种非内皮细胞，如周细胞、星形胶质细胞、脉络丛上皮细胞、心室室管膜细胞和神经元。关于它们的神经元表达，表明两种转运蛋白都位于特定的神经细胞群中，这些神经细胞群对于嘌呤能细胞信号传导的三种推定的细胞标志物也是免疫阳性的，即5 '-核苷酸酶、腺苷脱氨酶和核苷三磷酸二磷酸水解酶-2。因此，我们推测ABCB 1和ABCC 1的神经元表达可能与腺苷能/嘌呤能神经调节有关。最后，在多个腺垂体细胞中观察到这两种转运蛋白。(C)2014爱思唯尔爱尔兰有限公司版权所有。
ATP-binding cassette (ABC) transporters play an increasing role in the understanding of pathologic peptide deposition in neurodegenerative diseases (NDs), such as Alzheimer's and Parkinson's. To describe the location of the most important ABC transporters for NDs in human brain tissue, we investigated ABCB1 and ABCC1 immunohistologically in the adult human brain and pituitary. Both transporters have similar but not identical expression patterns. In brain regions with an established blood-brain barrier (BBB), ABCB1 and ABCC1 were ubiquitously expressed in endothelial cells of the microvasculature and in a subset of larger blood vessels (mostly venules). Remarkably, both transporters were also found in fenestrated capillaries in circumventricular organs where the BBB is absent. Moreover, ABCB1 and ABCC1 were also expressed in various non-endothelia cells such as pericytes, astrocytes, choroid plexus epithelia, ventricle ependymal cells, and neurons. With regard to their neuronal expression it was shown that both transporters are located in specific nerve cell populations, which are also immunopositive for three putative cell markers of purinergic cell signalling, namely 5'-nucleotidase, adenosine deaminase and nucleoside triphosphate diphosphohydrolase-2. Therefore, we speculate that neuronal expression of ABCB1 and ABCC1 might be linked to adenosinergic/purinergic neuromodulation. Lastly, both transporters were observed in multiple adenohypophyseal cells. (C) 2014 Elsevier Ireland Ltd. All rights reserved.