MiR-483-3p improves learning and memory abilities via XPO1 in Alzheimer's disease.

Abstract

IntroductionAlzheimer's disease (AD), a common form of dementia, has been reported to influence 27 million individuals globally. Several risk factors including oxidative stress, gut microbiota imbalance, and cognitive activity are reported to be closely associated with the initiation or progression of AD. Although miR‐483‐3p was identified to be downregulated in AD patient serum. However, the biological role and mechanism of miR‐483‐3p remained unknown in AD. Here, we explored the role of miR‐483‐3p in AD.MethodsSprague–Dawley rats were injected with homocysteine (Hcy) to establish an AD animal model. The Morris water maze tests and contextual fear tests were conducted to assess the cognitive and memory abilities of rats. TUNEL staining was utilized to determine cell apoptosis. Luciferase reporter assay was used to evaluate the binding relation between miR‐483‐3p and exportin 1 (XPO1).ResultsHomocysteine treatment (400 μg/kg) induced the learning, cognitive and memory defects of rats. miR‐483‐3p was downregulated in Hcy‐treated rat hippocampus. Functionally, miR‐483‐3p alleviated cell apoptosis and impairments of learning and memory abilities in Hcy‐treated rats. In addition, miR‐483‐3p inhibited cell apoptosis and protein level of AD‐associated factors (APP, BACE1, and Aβ1‐42) in PC12 cells. In mechanism, miR‐483‐3p was confirmed to target XPO1 in PC12 cells. XPO1 displayed high level in rat hippocampus and was negatively correlated with miR‐483‐3p levels. Finally, XPO1 overexpression rescued the suppressive effect of miR‐483‐3p on cell apoptosis and protein levels of AD‐associated factors.ConclusionsmiR‐483‐3p alleviates neural cell apoptosis and impairments of learning and memory abilities by targeting XPO1 in AD.