Conclusions
miR-483-3p alleviates neural cell apoptosis and impairments of learning and memory abilities by targeting XPO1 in AD.
Methods
Sprague-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).
Results
Homocysteine 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. Conclusions: miR-483-3p alleviates neural cell apoptosis and impairments of learning and memory abilities by targeting XPO1 in AD.