Document Type
Article
Date of Original Version
2016
Department
Biomedical and Pharmaceutical Sciences
Abstract
Introduction: 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 con- ducted 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 methyl- ation 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.
Citation/Publisher Attribution
Eid, A., Bhiaqi, S. W., Renehan, W. E., and Zawia, N. H. (2016). Developmental lead exposure and lifespan alterations in epigenetic regulators and their correspondence to biomarkers of Alzheimer's disease. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, 2, 123-131. doi:10.1016/j.dadm.2016.02.002
Available at: http://dx.doi.org/10.1016/j.dadm.2016.02.002
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Comment
Aseel Eid, William E. Renehan and Nasser H. Zawia are affiliated with the Interdisciplinary Neuroscience Program and the George and Ann Ryan Institute for Neuroscience Program.