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正常成人大脑中水通道蛋白水通道分布与表达的系统研究。

A systematic study of the distribution and expression of aquaporin water channels in normal adult human brain.

作者信息

Adiele Reginald C, Tham Mylyne, Lucchinetti Claudia F, Popescu Bogdan F Gh

机构信息

Department of Podiatric Medicine, Surgery and Biomechanics, School of Podiatric Medicine, College of Podiatric Medicine, University of Texas, Rio Grande Valley, 2102 Treasure Hills Blvd, Harlingen, TX, 78550, USA.

Department of Anatomy and Cell Biology, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada.

出版信息

J Neurol. 2025 Aug 13;272(9):574. doi: 10.1007/s00415-025-13304-9.

Abstract

BACKGROUNDS

Water regulation in the central nervous system (CNS) is very important to maintain normal neurophysiological homeostasis and intracranial pressure, as well as during neuropathological conditions. Not only because of the rigidity and limited mobility of the brain encasement, but also the need to maintain an appropriate osmotic balance across the various fluid-filled brain compartments for normal neurological functions. Aquaporins (AQPs), a family of non-energy dependent, bidirectional water transport protein channels play a crucial role in the maintenance of water and electrolyte balance in the human brain and their distribution and expression in regions of the brain need to be characterized to definitively certify and associate their pathogenic role in neuropathological disorders.

RESULTS

We carried out a detailed and systematic study of aquaporin-1 (AQP1), aquaporin-4 (AQP4) and aquaporin-9 (AQP9) expression in neurologically normal, autopsy brain tissues from nine patients. Interestingly, AQP1 immunoreactivity was not observed in the ependymal cell layer and cortical gray matter (GM) despite glial fibrillary acidic protein (GFAP) immunoreactive astrocytes in these regions. However, AQP1 was preferentially but not exclusively expressed in the white matter (WM) regions of the CNS, including the subcortical cerebral and cerebellar WM, brainstem, spinal cord, and choroid plexus. AQP4 immunolabeling was detected in both GM and WM regions of the CNS examined with enhanced expression in the upper and deeper layers of the cerebral cortex, while AQP9 immunoreactivity was only detected in the choroid plexus co-localizing with AQP1.

CONCLUSIONS

This is the first detailed and sequential study of AQP water transport channels in all regions of the human brain. The data affirm the anatomical locations, corresponding to the physiological functions of the three major AQP (AQP1, AQP4, and AQP9) water transport protein channels found in the adult human brain.

摘要

背景

中枢神经系统(CNS)中的水调节对于维持正常的神经生理稳态和颅内压非常重要,在神经病理状态下也是如此。这不仅是因为脑壳的刚性和有限的可移动性,还因为需要在充满液体的各个脑区之间维持适当的渗透平衡以实现正常的神经功能。水通道蛋白(AQPs)是一类非能量依赖性的双向水转运蛋白通道家族,在维持人脑的水和电解质平衡中起关键作用,其在脑区的分布和表达需要进行表征,以明确证实并关联它们在神经病理疾病中的致病作用。

结果

我们对9例神经功能正常的尸检脑组织中 aquaporin-1(AQP1)、aquaporin-4(AQP4)和aquaporin-9(AQP9)的表达进行了详细而系统的研究。有趣的是,尽管这些区域存在胶质纤维酸性蛋白(GFAP)免疫反应性星形胶质细胞,但在室管膜细胞层和皮质灰质(GM)中未观察到AQP1免疫反应性。然而,AQP1优先但并非唯一地表达于中枢神经系统的白质(WM)区域,包括皮质下脑白质和小脑白质、脑干、脊髓和脉络丛。在检查的中枢神经系统的GM和WM区域均检测到AQP4免疫标记,在大脑皮质的上层和深层表达增强,而AQP9免疫反应性仅在与AQP1共定位的脉络丛中检测到。

结论

这是对人脑中所有区域的AQP水转运通道进行的首次详细而连贯的研究。数据证实了在成人大脑中发现的三种主要AQP(AQP1、AQP4和AQP9)水转运蛋白通道的解剖位置与其生理功能相对应。

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