Treadmill training improves cognitive function by increasing IGF2 targeted downregulation of miRNA-483

Abstract

Optimal exercise can promote the development of cognitive functions. Nevertheless, mechanisms that elicit these positive effects of exercise still need to be elucidated. Insulin-like growth factor 2 (IGF2) is known to act as a potent enhancer of memory and cognitive functions, whereas the mechanism by which IGF2 regulates cognitive functions in terms of moderate treadmill exercise remains largely vague. In the study, rats were subjected to low-, moderate-, and high-intensity treadmill training for 6 weeks. Then, the Morris water maze test was used to investigate spatial learning and memory ability in rats subjected to treadmill exercises of different intensities. Subsequently, gene chip and bioinformatics analyses were used to explore IGF2 and predict target microRNAs (miRNAs). Quantitative real-time polymerase chain reaction, western blot, and immunofluorescence analysis were performed to detect the levels of IGF2. Furthermore, IGF2-small interfering RNA, the miRNA-483-mimic, and the miRNA-483-inhibitor were transfected to determine the role of IGF2 and miRNA-483 in the growth of hippocampal neurons. The results of the Morris water maze test showed that moderate-intensity treadmill training enhanced cognitive functions; meanwhile, the expression of IGF2 was significantly upregulated in the hippocampus after moderate-intensity treadmill exercise. From databases, miRNA-483 was screened and predicted as the target gene of IGF2. Moreover, silencing IGF2 inhibited neurite growth in the hippocampus of rats, the miRNA-483-inhibitor ameliorated silencing IGF2 induced impairment of hippocampal neurons. These findings suggested that treadmill training could enhance cognitive functions, wherein the underlying mechanism involved an increase in the expression of IGF2 and downregulation of miRNA-483.