Genome-wide expression and methylation profiling in the aged rodent brain due to early-life Pb exposure and its relevance to aging

Remi Dosunmu; Hany Alashwal; Nasser H. Zawia

doi:10.1016/j.mad.2012.05.003

Genome-wide expression and methylation profiling in the aged rodent brain due to early-life Pb exposure and its relevance to aging

Remi Dosunmu, Hany Alashwal, Nasser H. Zawia

Research output: Contribution to journal › Article › peer-review

77 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	435-443
Number of pages	9
Journal	Mechanisms of Ageing and Development
Volume	133
Issue number	6
DOIs	https://doi.org/10.1016/j.mad.2012.05.003
Publication status	Published - Jun 2012
Externally published	Yes

Keywords

Aging
Gene expression
Methylation arrays
Pb (lead)

ASJC Scopus subject areas

Ageing
Developmental Biology

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10.1016/j.mad.2012.05.003

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title = "Genome-wide expression and methylation profiling in the aged rodent brain due to early-life Pb exposure and its relevance to aging",

abstract = "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.",

keywords = "Aging, Gene expression, Methylation arrays, Pb (lead)",

author = "Remi Dosunmu and Hany Alashwal and Zawia, {Nasser H.}",

note = "Funding Information: This research was supported by the Intramural Research Program of the National Institutes of Health (NIH) , National Institute of Environmental Health Sciences (NIEHS) and by grants ( ES013022 and AG027246 ) from the NIH awarded to NHZ. The research core facility was funded (P20RR016457) by the National Center for Research Resources (NCRR) , a component of NIH. ",

year = "2012",

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doi = "10.1016/j.mad.2012.05.003",

language = "English",

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AU - Dosunmu, Remi

AU - Alashwal, Hany

AU - Zawia, Nasser H.

N1 - Funding Information: This research was supported by the Intramural Research Program of the National Institutes of Health (NIH) , National Institute of Environmental Health Sciences (NIEHS) and by grants ( ES013022 and AG027246 ) from the NIH awarded to NHZ. The research core facility was funded (P20RR016457) by the National Center for Research Resources (NCRR) , a component of NIH.

PY - 2012/6

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N2 - 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.

AB - 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.

KW - Aging

KW - Gene expression

KW - Methylation arrays

KW - Pb (lead)

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Genome-wide expression and methylation profiling in the aged rodent brain due to early-life Pb exposure and its relevance to aging

Abstract

Keywords

ASJC Scopus subject areas

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