Aquaporin-4 deficiency down-regulates glutamate uptake and GLT-1 expression in astrocytes

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• 刊名：Molecular and Cellular Neuroscience
• 出版年：2007
• 期刊代码：173_10447431
• 类别：bio
• 出版时间：January 2007
• 卷：34
• 期：1
• 页码：34-39
• 文件大小：546 K

摘要

The role of aquaporin-4 in water transport has been extensively investigated, while little information exists regarding its contribution to astrocytic functions such as the action to glutamatergic transmission. Since aquaporin-4 has been detected widely co-localized with glutamate transporter 1 (GLT-1) and glutamate transporters also present water transport properties, we investigated the regulative role of aquporin-4 on glutamate transporter using primary cultured astrocytes from aquaporin-4 knockout (AQP4^−/−) mice. It was demonstrated that lack of aquaporin-4 down-regulated astrocytic expression of GLT-1 but not of glutamate/aspartate transporter (GLAST). The result from [³H]d,l-glutamate uptake analysis showed a lower uptake capability in AQP4^−/− astrocytes. Furthermore, MTT and LDH assays indicated less cellular toxicity induced by excessive glutamate in AQP4^−/− genotype. These findings provide direct evidences for the first time that aquaporin-4 plays an important role in the function of glutamate transporters. And the present study will improve our understanding of aquaporin-4-glutamanergic biology.