MiR-214-3p attenuates cognition defects via the inhibition of autophagy in SAMP8 mouse model of sporadic Alzheimer's disease.

The autophagy process is the major cellular degradation pathway for long-lived proteins and organelles. Dysfunction of autophagy may lead to several neurodegenerative disorders. However, the regulation and function of autophagy in sporadic Alzheimer's disease (SAD) remain unclear. In this study, we established SAMP8 mouse as a suitable SAD model and performed microarray profiling to identify miR-214-3p as a SAD associated microRNA that was downregulated in hippocampal neurons of SAMP8 mice upon the induction of autophagy. Furthermore, decreased miR-214-3p level was detected in cerebrospinal fluid from SAD patients. Overexpression of miR-214-3p in primary neurons from SAMP8 mice inhibited autophagy, demonstrated by decreased levels of LC3βII and Beclin1, and reduced number of GFP-LC3-positive autophagosome vesicles, and led to increased viability and decreased caspase-mediated apoptosis. Conversely, antagomiR-214-3p promoted autophagy and apoptosis in neurons from SAMP8 mice. Mechanistically, miR-214-3p negatively regulated Atg12 expression by targeting the 3'-untranslated region of Atg12. Treatment of SAMP8 mice with miR-214-3p attenuated neuronal apoptosis and improved behavioral performance. Taken together, these results suggest that miR-214-3p suppresses autophagy and alleviates hippocampal neuron apoptosis, which indicates that miR-214-3p represents a new potential neuroprotective factor for SAD.