AQUAPORIN-4 MAINTAINS EPENDYMAL INTEGRITY IN ADULT MICE

AQUAPORIN-4 MAINTAINS EPENDYMAL INTEGRITY IN ADULT MICE
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Aquaporin-4 维持成年小鼠室管膜完整性

DOI:
10.1016/j.neuroscience.2009.04.044
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发表时间:
2009-08-04
期刊:
影响因子:
3.3
通讯作者:
Hu, G.
Hu, G.
中科院分区:
医学3区
文献类型:
--
作者:
Li, X.;Kong, H.;Hu, G.

文献摘要

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室管膜细胞形成脑室壁,并参与脑脊液(CSF)的产生。水通道蛋白-4(AQP 4)是脑的主要水通道,仅限于室管膜细胞的基底外侧质膜。AQP 4的高度极化表达表明其可能参与维持室管膜的结构和功能完整性。该假设通过使用我们实验室产生的成年AQP 4敲除小鼠来验证[Fan Y,Zhang J,Sun XL,Gao L,Zeng XN,Ding JH,Cao C,Niu L,Hu G(2005)Sex-and region-specific alterations of basal amino acid and monoamine metabolism in the brain of aquaporin-4 knockout mice. J Neurosci Res 82:458-464]。组织学分析显示AQP 4缺陷小鼠侧脑室和导水管室管膜层紊乱。大多数(92.7%)的裸小鼠表现出侧脑室容积减少,而一小部分(7.3%)有扩大或正常的脑室大小与狭窄的导水管。免疫组化结果显示AQP 4缺失导致室管膜细胞缝隙连接蛋白connexin 43表达减少。电子显微镜证实室管膜细胞的基底外侧膜缺乏连接复合物。此外,与野生型小鼠相比,AQP 4基因敲除小鼠的CSF产量减少,脑含水量增加。这些结果强调了AQP 4在维持室管膜结构和功能中的关键作用。此外,在成年AQP 4基因敲除小鼠中心室系统的可变轮廓表明AQP 4的功能多态性。(C)2009年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Ependymal cells form the walls of the ventricles, and take part in the production of cerebrospinal fluid (CSF). Aquaporin-4 (AQP4), a predominant water channel of the brain, is restricted to basolateral plasma membranes of ependymal cells. The highly polarized expression of AQP4 suggests it may be involved in maintaining the structural and functional integrity of the ependyma. This hypothesis was validated by using adult AQP4 knockout mice generated by our laboratory [Fan Y, Zhang J, Sun XL, Gao L, Zeng XN, Ding JH, Cao C, Niu L, Hu G (2005) Sex- and region-specific alterations of basal amino acid and monoamine metabolism in the brain of aquaporin-4 knockout mice. J Neurosci Res 82:458-464]. Histological analysis showed disorganized ependymal layer of the lateral ventricle and aqueduct in AQP4-deficiency mice. A majority (92.7%) of null mice displayed reduced lateral ventricular volume, while a small fraction (7.3%) had enlarged or normal ventricular size with a narrow aqueduct. Immunohistochemistry demonstrated that AQP4 deletion resulted in decreased expression of gap junction protein connexin43 in the ependymal cells. Electron microscopy confirmed junctional complex absence at basolateral membranes of ependynnocytes. Moreover, AQP4 knockout mice showed decreased CSF production and increased brain water content compared with wild-type mice. These results highlight a key role of AQP4 in maintaining the structure and function of the ependyma. In addition, variable profiles of ventricle system in adult AQP4 null mice indicate functional AQP4 polymorphisms. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.