Benshuai Yu1, Junzhu Zhang2, Hai Li3, Xiaohong Sun4. 1. Department of Neurology, The Fourth Affiliated Hospital of China Medical University, Shenyang 117000, PR China; Department of Neurosurgery, Benxi Central Hospital, Benxi 117000, PR China. 2. Department of Occupational Medicine, Benxi Central Hospital, Benxi 117000, PR China. 3. Department of Urology Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, PR China. 4. Department of Neurology, The Fourth Affiliated Hospital of China Medical University, Shenyang 117000, PR China. Electronic address: xhsun@cmu.edu.cn.
Abstract
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.
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.