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

Benshuai Yu, Junzhu Zhang, Hai Li, Xiaohong Sun
Gene 2020 June 12, : 144904

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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 promoted neuronal apoptosis by inhibiting the Wnt signaling pathway, thereby damaging the cognitive function.

CONCLUSIONS: AQP1 silencing attenuates the cognitive impairment in AD through activation of the Wnt signaling pathway, highlighting a novel therapeutic target against AD.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"