Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10956529 | Molecular and Cellular Neuroscience | 2012 | 9 Pages |
Abstract
It has been demonstrated that the water channel protein aquaporin-4 (AQP4) plays an important role in astrocyte plasticity in response to a variety of injuries or stimuli. However, the potential role of AQP4 in astrocyte response to β-amyloid (Aβ) has not been studied. The purpose of this study was to investigate this issue. Compared to media control, the lower concentrations of Aβ1-42 (0.1-1 μM) increased AQP4 expression in cultured mouse cortical astrocytes, while the higher concentrations of Aβ1-42 (10 μM) decreased AQP4 expression. AQP4 gene knockout reduced Aβ1-42-induced astrocyte activation and apoptosis, which was associated with a reduction in the uptake of Aβ via decreased upregulation of low-density lipoprotein receptor related protein-1. Moreover, time-course and levels of Aβ1-42-induced mitogen-activated protein kinase phosphorylation were altered in AQP4 null astrocytes compared with wild-type controls. Our data reveal a novel role of AQP4 in the uptake of Aβ by astrocytes, indicating that AQP4 is a molecular target for Alzheimer's disease.
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Authors
Wei Yang, Qi Wu, Chan Yuan, Junying Gao, Ming Xiao, Minxia Gu, Jiong Ding, Gang Hu,