EFFECTS OF EARLY THIAMINE INTERVENTION ON DNA METHYLATION AND Aβ NEUROTOXICITY IN HIPPOCAMPAL NEURON CELLS
Objective To explore the effects of early thiamine intervention on DNA methylation and intervention Aβ neurotoxicity in hippocampal neuron cells(HNCs).Methods HNCs from neonatal rats were cultured in vitro,and randomly divided into blank group,model group and low,medium and high dose groups of thiamine intervention.The HNCS were treated with different doses of thiamine for 3 days.The whole DNA methylation level of HNCs was determined by HPLC.The promoter methylation of CaMKIIα and GluR-2 genes was detected using MassARRAY.The cells were cultured in blank B27 medium until the cells matured.The effects of Aβ1-42 on the proliferation rate(PR%)and apoptosis rate(AR%)of HNCS were studied.Results(1)The DNA methylation level of HNCs early exposed to thiamine treatment was lower than the blank group,and the medium dose group showed a significant difference(P＜0.05).(2)Compared with the blank group,the methylation level of CaMKIIα promoter CpG 3,11 in the low dose thiamine group decreased significantly(P＜0.05),and the methylation level of GluR-2 promoter CpG5,23 increased significantly(P＜0.05).(3)The treatment of Aβ1-42 caused a decreased cell proliferation rate and increased apoptosis rate.Compared with the model group,early thiamine intervention could increase proliferation rate.The high dose group was higher than the low and medium dose groups(P＜0.05).Compared with the model group,early thiamine intervention could decrease apoptosis rate(P＜0.05).There were no significant differences(P＞0.05)between different thiamine intervention groups.Conclusion Early thiamine intervention can regulate the methylation level of HNCs,and protect against the Aβ neurotoxicity of mature hippocampal neuron cells through reducing the methylation level of CaMKIIα promoter.
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