MiR-216a-5p ameliorates learning-memory deficits and neuroinflammatory response of Alzheimer's disease mice via regulation of HMGB1/NF-κB signaling.

OBJECTIVE

The objective of this study was to explore whether miR-216a-5p could affect the learning-memory ability and inflammatory response of Alzheimer's disease (AD) mice via regulation of the HMGB1/NF-κB pathway.

METHODS

Mice were divided into the normal (wild-type C57BL/6 mice), AD (APP/PS1 double-transgenic mice), AD + miR-216a-5p, and AD + vector groups. The Morris water maze test was used to examine learning and memory ability. Nissl staining and TUNEL staining were performed to observe the survival and apoptosis of hippocampal neurons. In addition, Aβ deposition and the expression of inflammatory cytokines were determined, while miR-216a-5p expression and HMGB1/NF-κB pathway-related proteins were detected by qRT-PCR and Western blotting, respectively.

RESULTS

AD mice exhibited decreased miR-216a-5p expression but increased HMGB-1 protein expression in the hippocampus, and these mice had a prolonged escape latency, fewer number of times crossing the platform location and shortened time in the target quadrant compared to those in normal mice. AD mice also had an elevated number of TUNEL-positive cells, increased deposition of Aβ, increased expression of inflammatory cytokines and decreased number of Nissl-positive cells. In addition, AD mice presented with downregulated expression of cytoplasmic NF-κB p65 protein but upregulated expression of nuclear NF-κB p65 protein. However, AD mice treated with miR-216a-5p exhibited significant improvements of the abovementioned parameters. The dual-luciferase reporter assay confirmed that HMGB1 is a target gene of miR-216a-5p.

CONCLUSION

MiR-216a-5p can improve learning-memory ability and attenuate the inflammatory response of AD mice through targeted inhibition of the HMGB1/NF-κB pathway.