Several reports have shown that methyl CpG-binding protein 2 (MeCP2), brain-derived neurotrophic factor (BDNF), phospho-cAMP response element-binding protein (p-CREB) and microRNAs may be important in regulating academic performance because of their roles in neuropsychiatry and cognitive diseases. The first goal of this study was to explore the associations among MeCP2, BDNF, CREB and academic performance. This study also examined the pathway responsible for the effects of MeCP2, BDNF, p-CREB and microRNAs on academic performance. Scores from the basic competency test, an annual national competitive entrance examination, were used to evaluate academic performance. Subjects' plasma RNA was extracted and analyzed. This study determined that participants in the higher academic performance group had a significant difference in MECP2 mRNA expression compared with the lower academic performance group. We then used neuronal human derived neuroblastoma cell line (SH-SY5Y) cells with inducible MeCP2 expression from a second copy of the gene as a gain-of-function model and found that MeCP2 overexpression positively affected p-CREB and BDNF expression initially. After negative feedback, the p-CREB and BDNF levels subsequently decreased. In the neuronal phenotype examination, we found a significant reduction in total outgrowth and branches in MeCP2-induced cells compared with noninduced cells. This work describes pathways that may be responsible for the effects of MeCP2, BDNF, p-CREB and microRNAs on academic performance. These results may shed light on the development of promising clinical treatment strategies in the area of neuropsychological adjustment.
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