Open AccessDevelopmental lead exposure and lifespan alterations in epigenetic regulators and their correspondence to biomarkers of Alzheimer's disease
Author(s) -
Eid Aseel,
Bihaqi Syed Waseem,
Renehan William E.,
Zawia Nasser H.
Publication year - 2016
Publication title -
alzheimer's and dementia: diagnosis, assessment and disease monitoring
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.497
H-Index - 37
ISSN - 2352-8729
DOI - 10.1016/j.dadm.2016.02.002
Subject(s) - mecp2 , epigenetics , histone , western blot , biology , dna methylation , alzheimer's disease , methylation , disease , gene expression , medicine , genetics , gene , phenotype
Early life lead (Pb) exposure results in a latent increase in Alzheimer's disease (AD)–related proteins, and cognitive deficits late in life in both rodents and primates. This study was conducted to investigate if these late life changes were accompanied by epigenetic alterations. 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. 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.