Silencing of aquaporin1 activates the Wnt signaling pathway to improve cognitive function in a mouse model of Alzheimer's disease

Gene
Benshuai YuXiaohong Sun

Abstract

Aquaporins (AQPs) are water channel proteins robustly presenting in the central nervous system (CNS). Increasing evidence suggests the crucial role of AQP1 in the pathogenesis of CNS injury but scarce data are provided for the potential role of AQP1 in Alzheimer's disease (AD). Thus, the present study aimed to investigate the effects of AQP1 on cognitive function in a mouse model of AD. A mouse model of AD was established by using the β-amyloid isoform Aβ1-42, and then assessed by the step-through test and water maze experiment. The expression of AQP1 was quantified in the AD model. The effects of AQP1 on the cognitive function of AD mice and the Wnt signaling pathway were elucidated using gain- and loss-of-function approaches. Furthermore, hippocampal neurons were isolated and treated with Aβ1-42 for in vitro experiments and the effects of the Wnt signaling pathway on hippocampal neuron apoptosis were analyzed with the use of inhibitor or activator of this pathway. AQP1 was highly-expressed in the AD mouse model while AQP1 silencing improved cognitive function in AD mice. Besides, silencing of AQP1 exhibited protective effects on hippocampal neurons in AD mice. Furthermore, AQP1 inhibited the Wnt signaling pathway while AQP1 p...Continue Reading

Citations

May 1, 2021·International Journal of Molecular Sciences·Silvia MuccioliRoberto Costa
Aug 1, 2021·Expert Opinion on Drug Discovery·Ramón CacabelosVinogran Naidoo

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