PDF(Pubmed)
Abstract：
More than 20 years have passed since the first demonstration of Aquaporin-9 (AQP9) in the brain. Yet its precise localization and function in brain tissue remain unresolved. In peripheral tissues, AQP9 is expressed in leukocytes where it is involved in systemic inflammation processes. In this study, we hypothesized that AQP9 plays a proinflammatory role in the brain, analogous to its role in the periphery. We also explored whether Aqp9 is expressed in microglial cells, which would be supportive of this hypothesis. Our results show that targeted deletion of Aqp9 significantly suppressed the inflammatory response to the parkinsonian toxin 1-methyl-4-phenylpyridinium (MPP+). This toxin induces a strong inflammatory response in brain. After intrastriatal injections of MPP+, the increase in transcript levels of proinflammatory genes was less pronounced in AQP9-/- mice compared with wild-type controls. Further, in isolated cell subsets, validated by flow cytometry we demonstrated that Aqp9 transcripts are expressed in microglial cells, albeit at lower concentrations than in astrocytes. The present analysis provides novel insight into the role of AQP9 in the brain and opens new avenues for research in the field of neuroinflammation and chronic neurodegenerative disease.
摘要：
自首次在大脑中展示水通道蛋白9（AQP9）以来，已经过去了20多年。然而，其在脑组织中的精确定位和功能仍未解决。在外周组织中，AQP9在参与全身炎症过程的白细胞中表达。在这项研究中,我们假设AQP9在大脑中起促炎作用，类似于它在外围的作用。我们还探索了Aqp9是否在小胶质细胞中表达，这将支持这一假设。我们的结果表明，Aqp9的靶向缺失显着抑制了对帕金森病毒素1-甲基-4-苯基吡啶（MPP）的炎症反应。这种毒素在脑中诱导强烈的炎症反应。行纹状体内注射MPP+后，与野生型对照相比,AQP9-/-小鼠中促炎基因转录水平的增加不太明显.Further,在孤立的细胞亚群中，通过流式细胞术验证，我们证明Aqp9转录本在小胶质细胞中表达，尽管浓度低于星形胶质细胞。本分析为AQP9在大脑中的作用提供了新的见解，并为神经炎症和慢性神经退行性疾病领域的研究开辟了新的途径。
