title: Developmental lead exposure and lifespan alterations in epigenetic regulators and their correspondence to biomarkers of Alzheimer's disease.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Neurodegeneration Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, USA; Interdisciplinary Neuroscience Program, University of Rhode Island, Kingston, RI, USA; Geroge and Ann Ryan Institute for Neuroscience, University of Rhode Island, Kingston RI, USA.
authors.forename: Aseel
authors.initials: A
authors.lastname: Eid
authors.affiliation: Department of Pharmacology and Toxicology, University of Hail, Hail, Kingdom of Saudi Arabia.
authors.forename: Syed Waseem
authors.initials: SW
authors.lastname: Bihaqi
authors.affiliation: Neurodegeneration Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, USA; Interdisciplinary Neuroscience Program, University of Rhode Island, Kingston, RI, USA; Geroge and Ann Ryan Institute for Neuroscience, University of Rhode Island, Kingston RI, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Renehan
authors.affiliation: Neurodegeneration Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, USA; Interdisciplinary Neuroscience Program, University of Rhode Island, Kingston, RI, USA; Geroge and Ann Ryan Institute for Neuroscience, University of Rhode Island, Kingston RI, USA.
authors.forename: Nasser H
authors.initials: NH
authors.lastname: Zawia
keywords: Aging; Alzheimer's disease; Epigenetics; Lead (Pb); Lifespan