Effects of microRNA‐10a on synapse remodeling in hippocampal neurons and neuronal cell proliferation and apoptosis through the BDNF‐TrkB signaling pathway in a rat model of Alzheimer's disease

The aim of this study was to research the effects of microRNA‐10a (miR‐10a) on synapse remodeling and neuronal cells in rats with Alzheimer's disease (AD) through BDNF‐TrkB signaling pathway. Rat models of AD were established. The neuronal cells were allocated into blank, negative control (NC), miR‐10a mimics, miR‐10a inhibitors, K252a, and miR‐10a inhibitors + K252a groups. Expressions of miR‐10a, p38, PSD95, BDNF, cAMP‐response element‐binding protein (CREB), and tropomyosin receptor kinase B (TrκB) were tested using RT‐qPCR and Western blotting. Neuron cell proliferation, cycle, and apoptosis were observed using Cell counting kit‐8 (CCK8) assay and flow cytometry. The ultrastructure was observed under a scanning electron microscope. The miR‐10a expression of AD rats increased while p38, PSD95, BDNF, CREB, and TrκB expression decreased compared with the normal rats. Dual luciferase reporter gene assay testified miR‐10a targeted BDNF. The expressions of p38, PSD95, BDNF, CREB, and TrκB decreased in the miR‐10a mimics and K252a groups. Compared with the blank and NC group, the miR‐10a mimics and K252a groups showed inhibited cell growth rate with cells mainly rest in the G1 satge, and increased spoptosis. The miR‐10a inhibitors group presented an opposite trend to the miR‐10a mimics and K252a groups. The synapse was complete and abundant in the miR‐10a inhibitors group while disappeared in the miR‐10a mimics and K252a groups. The results indicated that miR‐10a restrains synapse remodeling and neuronal cell proliferation while promoting apoptosis in AD rats via inhibiting BDNF‐TrkB signaling pathway. To sum up, our study identified that miR‐10a overexpression inhibits the synapse remodeling in the hippocampus neurons of AD rats and inhibits proliferation and promotes apoptosis of neuronal cells through restraining the BDNF signaling pathway. The detailed mechanism of miR‐10a regulating BDNF in AD rat hippocampus remains to be investigated in the future.