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ATP结合盒转运蛋白ABCB1和ABCC1在老年人类大脑和垂体中的血管及血管外分布

Vascular and extravascular distribution of the ATP-binding cassette transporters ABCB1 and ABCC1 in aged human brain and pituitary.

作者信息

Bernstein Hans-Gert, Hölzl Gloria, Dobrowolny Henrik, Hildebrandt Jens, Trübner Kurt, Krohn Markus, Bogerts Bernhard, Pahnke Jens

机构信息

Department of Psychiatry, University of Magdeburg, Magdeburg, Germany.

Department of Psychiatry, University of Magdeburg, Magdeburg, Germany.

出版信息

Mech Ageing Dev. 2014 Nov-Dec;141-142:12-21. doi: 10.1016/j.mad.2014.08.003. Epub 2014 Sep 10.

Abstract

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.

摘要

ATP结合盒(ABC)转运蛋白在理解神经退行性疾病(NDs)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。为了描述人类脑组织中对NDs最重要的ABC转运蛋白的定位,我们对成人大脑和垂体进行了ABCB1和ABCC1的免疫组织学研究。这两种转运蛋白具有相似但不完全相同的表达模式。在具有成熟血脑屏障(BBB)的脑区,ABCB1和ABCC1在微脉管系统的内皮细胞以及一部分较大血管(主要是小静脉)中普遍表达。值得注意的是,在没有BBB的室周器官的有孔毛细血管中也发现了这两种转运蛋白。此外,ABCB1和ABCC1也在各种非内皮细胞中表达,如周细胞、星形胶质细胞、脉络丛上皮细胞、脑室室管膜细胞和神经元。关于它们在神经元中的表达,研究表明这两种转运蛋白位于特定的神经细胞群体中,这些群体对嘌呤能细胞信号传导的三种假定细胞标志物,即5'-核苷酸酶、腺苷脱氨酶和核苷三磷酸二磷酸水解酶-2也呈免疫阳性。因此,我们推测ABCB1和ABCC1在神经元中的表达可能与腺苷能/嘌呤能神经调节有关。最后,在多个腺垂体细胞中观察到了这两种转运蛋白。

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