Histological Methylation Mechanism Of Learning And Memory Damage In Rats With Chronic Lead Exposure

Lead(Pb²⁺)is a pervasive environmental threat to human health,and primarily exerted its detrimental effects on the nervous system.Although remarkable progress has been made in the elucidation of Pb's neurotoxicity,the precise molecular mechanisms underlying this widespread intoxication still remains elusive.Epigenetics is a bridge between environmental factors and genetic factors,It's role in the process of learning function damage induced by lead exposure is not clear.Objective:1.Clarify the key role played by EZH2 and H3K27me3 in the process of learning function damage induced by lead exposure.2.To investigate the mechanism of chronic lead exposure in reducing H3K27me3 levels.3.To explore the mechanism of lead exposure affecting Wnt signaling pathway through H3K27me3.Methods:1.We use PC12 cells as the neurocellar model and we explore the key role played by EZH2 in the process of learning function damage induced by lead exposure use the Chip method.2.We use Co-IP to clarify that Pb exposure reduced the level of H3K27me3 in neurons by EZH2.3.Morris water maze experiments was performed at 10 weeks and Golgi-cox staining method was used to observe the dendritic spine morphology,these experiments can clarify the effect of reducing H3 level on learning and memory function.4.We use Chip-on-chip to explore the abnormalities of H3K27me3 on the regulation of gene expression.Results: 1.EZH2 emerges as a central player to regulate lead-led neurotoxicity in a transcriptionally dependent and independent manner.2.Pb exposure reduced the level of H3K27me3 in neurons by EZH2,which directly lead to the damage of learning and memory function.3.Lead exposure changes the regulation of H3K27me3 on the expression of several Wnt signaling proteins.Conclusion: Pb exposure reduced the level of H3K27me3 in neurons by EZH2 is the main reason of the damage of learning and memory function.In this process,the regulation of H3K27me3 on the expression of several Wnt signaling proteins play the most critical role.