Objective: To investigate the effect of IMPX977 on MeCP2 targeted-genes and the feasibility of IMPX977 acting as a therapeutic candidate drug for Rett syndrome by genomewide transcription profiling.Methods: Rats' cortex of control group, IMPX977-treated low-dose group(10 mg/kg), and IMPX977-treated high-dose group(30 mg/kg) were collected and RNA was extracted from the tissues. Then, RNA was subjected to RNA-sequencing. Gene ontology(GO) and kyoto encyclopedia of genes and genomes(KEGG)were used in functional enrichment analysis of differentially expressed genes.Results: Six MeCP2 targeted-genes were identified in the low/control categories, but not in the high/control categories.Conclusion: Low-dose treatment of IMPX977(10 mg/kg) showed a positive effect on MeCP2 targeted-genes and it may serve as a drug candidate for Rett syndrome therapy with proper dosage.
Ying ZhaoLiang LeYue-qiang SongLi-xin QiHui FuXue BaiSi-guang LiXin-sheng NanKe-ping Hu
Objective To investigate the effect of IMPX977 on methyl-Cp G-binding protein 2（MeCP2） expression in rats. Methods Forty-eight SD rats were randomly divided into four groups： normal control group, olive oil（negative control, 5 mL/kg oil） group, and 10 mg/kg and 30 mg/kg IMPX977 administration groups. All rats were given corresponding dose of drugs each other day and administered orally for two weeks. Tissues including cortex and cerebellum were collected from rats to assay the expression of MeCP2 by quantitative RT-PCR and Western blotting. Results The IMPX977 supplement showed no significant effect on the body weight of rats. In normal rats, MeCP2 was highly expressed in cerebellum, cortex and hippocampus, and less expressed in heart, spleen and lung. In addition to male rats, compared with the control group, the expression of MeCP2 mRNA was significantly increased in cerebellum after 30 mg/kg IMPX977 treatment and contrarily, absolutely decreased in cortex of all treatment groups. Furthermore, in female rats MeCP2 mRNA was reduced in cortex of both olive oil and 30 mg/kg IMPX977 treatment groups compared with control group. Meanwhile, MeCP2 protein level was significantly elevated in cerebellum of treated male rats compared to the control group. In contrast to the control group, the expression of MeCP2 protein in both cerebellum and cortex of female rats in other three groups was increased. Conclusion IMPX977 treatment（10 mg/kg） may elevate the expression of MeCP2, which establishes experimental foundation for the further research on rat models of Rett syndrome.
Ya HuLiang LeLi-xin QiYing ZhaoHui FuChen DuanXiao-ying WangKe-ping Hu
