Comprehensive Evaluation on Effect of IMPX977 on Expression of Methyl-CpG-binding Protein 2 in Rats

Abstract

ObjectiveTo investigate the effect of IMPX977 on methyl-CpG-binding protein 2 (MeCP2) expression in rats. MethodsForty-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. ResultsThe 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. ConclusionIMPX977 treatment (10 mg/kg) may elevate the expression of MeCP2, which establishes experimental foundation for the further research on rat models of Rett syndrome.