miR-199a decreases Neuritin expression involved in the development of Alzheimer's disease in APP/PS1 mice

Neuritin plays an important role in neural development and plasticity. A recent study demonstrated that increasing Neuritin levels attenuated synaptic damage in mice with Alzheimer's disease (AD), which exhibit a decreased Neuritin expression. However, it remains unclear as to whether Neuritin expression is regulated by microRNAs (miRNAs or miRs) in AD. In the present study, it was found that miR-199a decreased Neuritin expression and was therefore involved in the development of AD. Subsequently, differentially expressed miRNAs in AD from datasets and the literature were recruited, and those that could bind Neuritin were predicted using bioinformatics analysis. The present study then focused on the candidate miRNAs that were highly associated with Neuritin and were upregulated in AD. The expression patterns of the candidate miRNAs and Neuritin in the hippocampus and cortex of APP/PS1 (AD model) mice at different stages were then detected and analyzed. It was found that miR-199a expression was significantly increased in the early stages of AD and was negatively associated with Neuritin expression. Furthermore, it was revealed that the decreased Neuritin expression was due to the direct targeting of the Neuritin 3′-UTR by miR-199a. Finally, the association between the spatial memory capacity of APP/PS1 mice and the changes in miR-199a and Neuritin expression protein was investigated. On the whole, the data of the present study suggest that miR-199a is involved in the development of AD by regulating Neuritin expression.