Aquaporin-4 Mediates the Suppressive Effect of Lipopolysaccharide on Hippocampal Neurogenesis
Aquaporin-4 Mediates the Suppressive Effect of Lipopolysaccharide on Hippocampal Neurogenesis
复制标题
Aquaporin-4 介导脂多糖对海马神经发生的抑制作用。
DOI：
10.1159/000467141
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发表时间：
2016-01-01
影响因子：
2.4
通讯作者：
Fan, Yi
中科院分区：
文献类型：
--
作者：
Liang, Rui;Yong, Shoulei;Fan, Yi
目的：水通道蛋白-4（AQP 4）是脑内水平衡的关键分子，与成体神经发生有关，但其调节成体神经干细胞（aNSC）的机制仍未完全阐明。神经炎症对成人神经发生具有相关影响，这是各种神经退行性疾病的共同特征。考虑到神经炎症和AQP 4之间可能存在的联系，我们推测AQP 4可能介导胶质细胞中促炎细胞因子的合成和释放，进而间接调节成年海马神经发生。研究方法：利用AQP 4基因敲除小鼠，研究了AQP 4在脂多糖（LPS）诱导的神经炎症后海马神经发生中的作用。结果如下：我们意外地发现，AQP 4缺陷减弱了全身性LPS暴露后aNSC增殖的减少，伴随着海马中胶质细胞活化的抑制和促炎细胞因子的产生的抑制。同时，体内研究表明，脂多糖诱导激活的小胶质细胞不表达AQP 4，表明不可能直接调节AQP 4来激活小胶质细胞。此外，我们在体外证明，AQP 4缺乏抑制星形胶质细胞的活化，减少释放的促炎细胞因子从星形胶质细胞。结论：我们的数据表明，AQP 4介导的抑制作用，神经炎症对海马神经发生通过调节星形胶质细胞的反应。(C)2017 S. Karger AG，巴塞尔
Objective: Aquaporin-4 (AQP4), a key molecule for water homeostasis in the brain, is associated with adult neurogenesis, but its mechanisms regulating adult neural stem cells (aNSC) remain largely unexplored. Neuroinflammation has a relevant influence on adult neurogenesis, which is a common feature in various neurodegenerative diseases. Considering the possible link between neuroinflammation and AQP4, we speculate that AQP4 may mediate the synthesis and release of proinflammatory cytokines in glia and then indirectly regulate adult hippocampal neurogenesis. Methods: Using AQP4 knockout mice, we investigated the effects of AQP4 on hippocampal neurogenesis after lipopolysaccharide (LPS)-induced neuroinflammation. Results: We unexpectedly found that AQP4 deficiency attenuated the decrease in aNSC proliferation after systemic LPS exposure, accompanied by inhibition of glial activation and suppression of the production of proinflammatory cytokines in the hippocampus. Meanwhile, in vivo studies demonstrated that LPS-induced activated microglia did not express AQP4, indicating the impossibility of direct regulation of AQP4 to activate microglia. Furthermore, we demonstrated in vitro that AQP4 deficiency inhibited astrocyte activation and reduced the release of proinflammatory cytokines from astrocytes. Conclusion: Our data suggest that AQP4 mediates the suppressive effect of neuroinflammation on hippocampal neurogenesis via regulation of the astroglial response. (C) 2017 S. Karger AG, Basel