Aerobic exercise relieved vascular cognitive impairment via NF-κB/miR-503/BDNF pathway.

objectiveTo investigate the mechanism of aerobic exercise in the relief of vascular cognitive impairment (VCI). MATERIALS AND

methodsLatency of Water Maze test was measured at sham, 2VO, 2VO+EX groups. miR-503 and BDNF mRNA levels were detected by quantitative real-time PCR. Protein levels of NF-κB and BDNF were detected by Western blot. Hippocampal neuron cell apoptosis was detected by flow cytometry. Luciferase reporter assay was conducted to investigate the effect of miR-503 on BDNF.

resultsLatency of Water Maze test in 2VO group was longer than Sham group, while exercise shortened the latency. The expressions of NF-κB and miR-503 in 2VO group were higher than Sham group, while exercise downregulated the expressions. BDNF level in 2VO group were downregulated than Sham group, while exercise upregulated the levels. We also found NF-κB, miR-503 levels were upregulated and BDNF level was downregulated in OGD-treated hippocampal neuron cells. In addition, OGD increased the expression of NF-κB and miR-503, and the expression of miR-503 was downregulated when treated with NF-κB inhibitor (PDTC). Moreover, we confirmed BDNF was a direct target of miR-503. OGD decreased the expression of BDNF, while miR-503 inhibitor reversed this effect. And we proved OGD induced cell apoptosis via NF-κB/miR-503/BDNF. Finally, in rats injected with miR-503 inhibitor, latency of Water Maze test was shortened, miR-503 expression was downregulated, and BDNF level was upregulated. While in rats injected with miR-503 mimic, the results were the opposite.

conclusionAerobic exercise relieved VCI via NF-κB/miR-503/BDNF pathway.