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Maternal folate depletion and high-fat feeding from weaning affects DNA methylation and DNA repair in brain of adult offspring

Lookup NU author(s): Dr Sabine Langie, Sebastian Achterfeldt, Joanna GÓRNIAK, Rachel Godschalk, Dr Jill McKay, Professor John Mathers


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The mechanisms through which environmental and dietary factors modulate DNA repair are still unclear but may include dysregulation of gene expression due to altered epigenetic markings. In a mouse model, we investigated the effect of maternal folate depletion during pregnancy and lactation, and high-fat feeding from weaning, on base excision repair (BER) and DNA methylation and expression of selected BER-related genes in the brain of adult offspring. While folate depletion did not affect BER activity of the mothers, BER increased in the offspring at weaning (P0.052). In the long term, as observed in 6-mo-old offspring, the double insult, i.e., maternal low-folate supply and high-fat feeding from weaning, decreased BER activity significantly in the cortex, cerebellum, hippocampus, and subcortical regions (P<0.017). This fall in BER activity was associated with small changes in methylation or expression of BER related genes. Maternal folate depletion led to slightly increased oxidative DNA damage levels in subcortical regions of adult offspring, which may increase sensitivity to oxidative stress and predispose to neurological disorders. In summary, our data suggest that low-folate supply during early life may leave an epigenetic mark that can predispose the offspring to further dietary insults, causing adverse effects during adult life.

Publication metadata

Author(s): Langie SAS, Achterfeldt S, Gorniak JP, Halley-Hogg KJA, Oxley D, van Schooten FJ, Godschalk RWL, McKay JA, Mathers JC

Publication type: Article

Publication status: Published

Journal: FASEB Journal

Year: 2013

Volume: 27

Issue: 8

Pages: 3323-3334

Print publication date: 01/08/2013

Online publication date: 19/04/2013

ISSN (print): 0892-6638

ISSN (electronic): 1530-6860

Publisher: Federation of American Societies for Experimental Biology


DOI: 10.1096/fj.12-224121

PubMed id: 23603834

Notes: This article was accepted pending minor amendments on Feb 14th 2013.


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Funder referenceFunder name
Biotechnology and Biological Sciences Research Council (BBSRC)
Engineering and Physical Sciences Research Council
Lifelong Health and Wellbeing cross council initiative by the UK Medical Research Council
Economic and Social Research Council