Inhibition of circ_0004381 improves cognitive function via miR-647/PSEN1 axis in an Alzheimer disease mouse model

Circ_0004381 promotes neuronal damage in Parkinson disease, but its role in Alzheimer disease (AD) is unreported. The goal of this study was to investigate the role and potential mechanisms of circ_0004381 effects in AD models. Primary hippocampal neurons were treated with amyloid-beta (A beta 1-42) to construct AD cell models. We found that circ_0004381 was upregulated in A beta 1-42-treated hippocampal neurons. Knockdown of circ_0004381 attenuated A beta 1-42-induced apoptosis, oxidative stress, and mitochondrial dysfunction in hippocampal neurons. Next, we induced microglia activation with lipopolysaccharide (LPS). The results of flow cytometry experiments showed that knockdown of circ_0004381 promoted microglial M2-type polarization and knockdown of circ_0004381 inhibited the production of inflammatory factors by microglia. Furthermore, knockdown of circ_0004381 improved cognitive function of male APPswe/PS1dE9 transgenic mice. Mechanistically, circ_0004381 regulated presenilin-1 (PSEN1) expression by absorbing miR-647. MiR-647 inhibition attenuated the effects of circ_0004381 knockdown. In conclusion, knockdown of circ_0004381 attenuated hippocampal neuronal damage and promoted microglia M2-type polarization through the miR-647/PSEN1 axis, ultimately improving cognitive function in AD model mice.

Automated summary

The study found that circ_0004381 plays an important role in Alzheimer's disease models, and knockdown of circ_0004381 can attenuate hippocampal neuronal damage and promote microglia M2-type polarization through the miR-647/PSEN1 axis.