AQUAPORIN-4 MEDIATES COMMUNICATION BETWEEN ASTROCYTE AND MICROGLIA: IMPLICATIONS OF NEUROINFLAMMATION IN EXPERIMENTAL PARKINSON'S DISEASE
AQUAPORIN-4 MEDIATES COMMUNICATION BETWEEN ASTROCYTE AND MICROGLIA: IMPLICATIONS OF NEUROINFLAMMATION IN EXPERIMENTAL PARKINSON'S DISEASE
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DOI：
10.1016/j.neuroscience.2016.01.003
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发表时间：
2016-03-11
期刊：
影响因子：
3.3
通讯作者：
Hu, G.
中科院分区：
文献类型：
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作者：
Sun, H.;Liang, R.;Hu, G.
水通道蛋白-4（AQP 4）是一种水选择性膜转运蛋白，在包括帕金森病（PD）在内的各种炎症性病变中的星形胶质细胞中上调。然而，AQP 4在神经炎症中的确切功能作用仍然未知。在本研究中，我们研究了AQP 4如何参与PD的神经炎症使用AQP 4敲除（KO）小鼠和星形胶质细胞小胶质细胞共培养。我们发现，AQP 4基因敲除小鼠表现出增加的基础和诱导型典型NF-κ B活性，并表现出显着增强的神经胶质细胞增生（星形胶质细胞增生和小胶质细胞增生）在慢性MPTP（1-甲基-4-苯基-1，2，3，6-四氢吡啶）/丙磺舒PD模型，伴随着在中脑中的IL-1 β和TNF-α的生产增加。同样，在用MPP+（1-甲基-4-苯基吡啶）处理的中脑星形胶质细胞培养物中，AQP 4缺乏增强了NF-κ B通路的激活和IL-1 β和TNF-α的产生。此外，AQP 4缺陷促进了共培养系统中小胶质细胞的活化。我们的数据提供了第一个证据表明，AQP 4调节星形胶质细胞与小胶质细胞的通信在神经炎症，虽然其对星形胶质细胞炎症激活的影响仍有待探讨。(C)2016年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Aquaporin-4 (AQP4), a water-selective membrane transport protein, is up-regulated in astrocytes in various inflammatory lesions, including Parkinson disease (PD). However, the exact functional roles of AQP4 in neuroinflammation remain unknown. In the present study, we investigated how AQP4 participates in the neuroinflammation of PD using AQP4 knockout (KO) mice and astrocytemicroglial co-cultures. We found that AQP4 KO mice exhibited increased basal and inducible canonical NF-kappa B activity, and showed significantly enhanced gliosis (astrocytosis and microgliosis) in chronic MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)/probenecid PD models, companying with the increase in the production of IL-1 beta and TNF-alpha in the midbrain. Similarly, AQP4 deficiency augmented the activation of the NF-kappa B pathway and the production of IL-1 beta and TNF-alpha in midbrain astrocyte cultures treated with MPP+ (1-methyl-4-phenylpyridinium). Furthermore, AQP4 deficiency promoted activation of microglial cells in the co-cultured system. Our data provide the first evidence that AQP4 modulates astrocyte-to-microglia communication in neuroinflammation, although its effect on astrocyte inflammatory activation remains to be explored. (C) 2016 IBRO. Published by Elsevier Ltd. All rights reserved.