Abstract: Objective To investigate the relationship between CDKL5 and MeCP2 in the mechanism of Rett syndrome. Methods The primary cortical neurons that obtained from embryonic day 18 Sprague Dawley rat were transfected by effective small interfering RNAs to silence Cdkl5, dividing into Cdkl5 shRNA group and control shRNA group. The technology of real time-PCR and western blot were used to evaluate the efficiency of silenced gene and detect its influence on both Mecp2 and the related downstream target genes.. The cell viability was assessed by the value of optical density through CCK8. The state of cell apoptosis was investigated by the level of caspase3 and cleaved-caspase3 through real time-PCR and western blot. Results Compared with control shRNA group, transfection with effective Cdkl5 shRNA in neurons decreased Cdkl5 mRNA by 73% and Cdkl5 protein by 75% (p<0.05). Cdkl5 inhibition was related to more than 2-fold induction of Mecp2 both in mRNA and protein level (p<0.05). At the same time, the level of Bdnf XI transcript decreased while Psd95 increased in transfected neurons (p<0.05). Conclusions A stable model of Cdkl5 silenced neurons is established. This preliminary study suggests that CDKL5 may fulfill its duty on downstream target genes through regulating the function of MeCP2.

Key words: Rett syndrome, Cdkl5, Mecp2, Bdnf