Developmental lead exposure and lifespan alterations in epigenetic regulators and their correspondence to biomarkers of Alzheimer's disease

发育期铅暴露和寿命变化对表观遗传调节因子的影响及其与阿尔茨海默病生物标志物的对应关系

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作者:Aseel Eid, Syed Waseem Bihaqi, William E Renehan, Nasser H Zawia

Discussion

Epigenetic modifiers are affected by the developmental exposure to Pb and may play a role in mediating the latent increases in AD-related proteins in the brain.

Methods

Western blot analysis and RT-PCR were used to measure Deoxyribonucleic acid methylation regulators (DNMT1, DNMT3a, MeCP2, MAT2A) and histone proteins (H3K9Ac, H3K4me2, H3K27me3).

Results

Cerebral levels of DNMT1 and MeCP2 were significantly reduced in mice exposed to Pb early in life, whereas the expression of DNMT3a was not altered. Levels of MAT2a were increased in the Pb-exposed mice across the lifespan. H3K9Ac and H3K4me2, involved in gene activation, were decreased, whereas the repressive mark H3K27me3 was elevated.

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