Genome-wide expression and methylation profiling in the aged rodent brain due to early-life Pb exposure and its relevance to aging
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In this study, we assessed global gene expression patterns in adolescent mice exposed to lead (Pb) as infants and their aged siblings to identify reprogrammed genes. Global expression on postnatal day 20 and 700 was analyzed and genes that were down- and up-regulated (≥2 fold) were identified, clustered and analyzed for their relationship to DNA methylation. About 150 genes were differentially expressed in old age. In normal aging, we observed an up-regulation of genes related to the immune response, metal-binding, metabolism and transcription/transduction coupling. Prior exposure to Pb revealed a repression in these genes suggesting that disturbances in developmental stages of the brain compromise the ability to defend against age-related stressors, thus promoting the neurodegenerative process. Overexpression and repression of genes corresponded with their DNA methylation profile.
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There is evidence to implicate DNA methylation as a potential mechanism by which developmental lead exposure alters neurodevelopment and function throughout life.
“There is evidence to implicate DNA methylation as a potential mechanism by which developmental lead exposure alters neurodevelopment and function throughout life [ 121 , 122 ].”
From DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders? (2016) · cites this paper as [122]
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References 29 · Cited by 91
- Authors
- Dosunmu, R., Alashwal, H., & Zawia, N. H.
- Affiliations
- University of Rhode Island (US)
- Corresponding author
- Zawia, Nasser H.
- ORCID
- Alashwal, Hany
- Venue
- Mechanisms of Ageing and Development
- Publisher
- Elsevier BV
- Published
- 2012-06
- Volume
- 133
- Issue
- 6
- Pages
- 435-443
- ISSN
- 0047-6374 (ISSN-L)
- PMC
- PMC3389195
- OpenAlex
- W1998499959
- Cited by
- 91
- References
- 29
- Citations by year
- 2026: 1 · 2024: 6 · 2023: 6 · 2022: 8 · 2021: 8 · 2020: 7 · 2019: 4 · 2018: 6 · 2017: 11 · 2016: 8 · 2015: 9 · 2014: 8 · 2013: 6 · 2012: 2
- FWCI
- 5.55
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Mechanisms of Ageing and Development (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Journal of Media Literacy Education (submittedVersion, cc-by-nc-nd)
- Funders
- National Institute for Health and Care Research
- National Institutes of Health
- National Institute on Aging (R03AG027246, AG 027246)
- National Institute of Environmental Health Sciences (ES013022, R01ES015867, R21ES013022)
- National Center for Research Resources (P20RR016457)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Heavy Metal Exposure and Toxicity
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- lead exposure, brain aging, DNA methylation, gene expression profiling, neurodegeneration, immune response genes, gene reprogramming, postnatal development
- MeSH terms
- Aging, Alzheimer Disease, Animals, Brain, Environmental Exposure, Female, Lead, Male, Metalloproteins, Mice, Inbred C57BL, Down-Regulation, Up-Regulation, Genome, DNA Methylation, Gene Expression Profiling, Mice, Adaptive Immunity
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