Cited by 162Epigenetics and DNA MethylationHeavy Metal Exposure and ToxicityAlzheimer's disease research and treatments

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Infant exposure to lead (Pb) and epigenetic modifications in the aging primate brain: implications for Alzheimer’s disease

Bihaqi, Syed Waseem, Huang, Hui, Wu, Jinfang, Zawia, Nasser H.·2011·Journal of Alzheimer’s Disease

DOI 10.3233/jad-2011-111013

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Abstract

The beginnings of late onset Alzheimer's disease (LOAD) are still unknown; however, the progressive and latent nature of neurodegeneration suggests that the triggering event occurs earlier in life. Aging primates exposed to lead (Pb) as infants exhibited an overexpression of the amyloid-β protein precursor (AβPP), amyloid-β (Aβ) and enhanced pathologic neurodegeneration. In this study, we measured the latent expression of a wide array of brain-specific genes and explored whether epigenetic pathways mediated such latent molecular and pathological changes. We analyzed the levels of proteins associated with DNA methylation, i.e., DNA methyltransferase 1 (Dnmt1), DNA methyltransferase3a (Dnmt3a), methyl-CpG binding protein-2 (MeCP2) and those involved in histone modifications (acetylated and methylated histones). We monitored the expression profiles of these intermediates across the lifespan and analyzed their levels in 23-year-old primate brains exposed to Pb as infants. Developmental Pb exposure altered the gene expression of the arrayed genes, which were predominately repressed, with fewer upregulated genes. The latent induction and repression of genes was accompanied by a significant decrease in the protein levels of Dnmts, MeCP2, and proteins involved in histone modifications. The attenuation of DNA methylation enzymes is consistent with hypomethylating effects, which promote upregulation of the genes, while the alterations in the histone modifiers are associated with the repression of genes. Hence, we deduce that early life exposure to Pb can reprogram gene expression resulting in both upregulation and down-regulation of genes through alternate epigenetic pathways contributing to an enhancement in neurodegeneration in old age.

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Dignam, J. D., Lebovitz, R. M., & Roeder, R. G. (1983) · Nucleic Acids Research · doi:10.1093/nar/11.5.1475 · Cited by 11,262
The language of covalent histone modifications
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Jones, P. L., Veenstra, G. J. C., Wade, P. A., Vermaak, D., Kass, S. U., Landsberger, N., Strouboulis, J., & Wolffe, A. P. (1998) · Nature Genetics · doi:10.1038/561 · Cited by 2,791
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Authors: Bihaqi, S. W., Huang, H., Wu, J., & Zawia, N. H.
Affiliations: University of Rhode Island (US)
Zhengzhou University (CN)
ORCID: Bihaqi, Syed Waseem
Huang, Hui
Wu, Jinfang
Venue: Journal of Alzheimer’s Disease
Publisher: SAGE Publications
Published: 2011-12-12
Volume: 27
Issue: 4
Pages: 819-833
ISSN: 1387-2877 (ISSN-L)
1875-8908
DOI: 10.3233/jad-2011-111013
OpenAlex: W1693568153
Cited by: 162
References: 60
Citations by year: 2026: 5 · 2025: 5 · 2024: 7 · 2023: 8 · 2022: 6 · 2021: 10 · 2020: 14 · 2019: 14 · 2018: 10 · 2017: 12 · 2016: 15 · 2015: 12 · 2014: 19 · 2013: 14 · 2012: 10
FWCI: 5.72
Type: journal article
Language: en
Open access: closed
Licence: journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations: Journal of Alzheimer s Disease (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute for Health and Care Research
Institute of Environmental Science and Research
National Institute of Environmental Research
National Institutes of Health
National Institute of Environmental Health Sciences (R01ES015867)
National Center for Research Resources (P20RR016457)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Heavy Metal Exposure and Toxicity
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Keywords: lead exposure
MeSH terms: Age Factors, Aging, Animals, Animals, Newborn, Disease Models, Animal, Female, Humans, Lead, Lead Poisoning, Macaca fascicularis, Nerve Tissue Proteins, RNA, Messenger, Transcription Factors, DNA Modification Methylases, Cohort Studies, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, DNA Methylation, rab5 GTP-Binding Proteins, Epigenesis, Genetic, Methyl-CpG-Binding Protein 2

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Infant exposure to lead (Pb) and epigenetic modifications in the aging primate brain: implications for Alzheimer’s disease

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