{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T22:01:52Z","timestamp":1792101712822,"version":"4.4.0"},"reference-count":82,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T00:00:00Z","timestamp":1709078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/G007993\/1"],"award-info":[{"award-number":["BB\/G007993\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010052","name":"Northumbria University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010052","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,4,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The developmental origins of health and disease hypothesis suggest early-life environment impacts health outcomes throughout the life course. In particular, epigenetic marks, including DNA methylation, are thought to be key mechanisms through which environmental exposures programme later-life health. Adequate maternal folate status before and during pregnancy is essential in the protection against neural tube defects, but data are emerging that suggest early-life folate exposures may also influence neurocognitive outcomes in childhood and, potentially, thereafter. Since folate is key to the supply of methyl donors for DNA methylation, we hypothesize that DNA methylation may be a mediating mechanism through which maternal folate influences neurocognitive outcomes. Using bisulphite sequencing, we measured DNA methylation of five genes (Art3, Rsp16, Tspo, Wnt16, and Pcdhb6) in the brain tissue of adult offspring of dams who were depleted of folate (n\u2005=\u20055, 0.4 mg folic acid\/kg diet) during pregnancy (~19\u201321 days) and lactation (mean 22 days) compared with controls (n\u2005=\u20056, 2 mg folic acid\/kg diet). Genes were selected as methylation of their promoters had previously been found to be altered by maternal folate intake in mice and humans across the life course, and because they have potential associations with neurocognitive outcomes. Maternal folate depletion was significantly associated with Art3 gene hypomethylation in subcortical brain tissue of adult mice at 28 weeks of age (mean decrease 6.2%, P\u2005=\u2005.03). For the other genes, no statistically significant differences were found between folate depleted and control groups. Given its association with neurocognitive outcomes, we suggest Art3 warrants further study in the context of lifecourse brain health. We have uncovered a potential biomarker that, once validated in accessible biospecimens and human context, may be useful to track the impact of early-life folate exposure on later-life neurocognitive health, and potentially be used to develop and monitor the effects of interventions.<\/jats:p>","DOI":"10.1093\/mutage\/geae007","type":"journal-article","created":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T23:55:21Z","timestamp":1709078121000},"page":"196-204","source":"Crossref","is-referenced-by-count":1,"title":["Influence of maternal folate depletion on Art3 DNA methylation in the murine adult brain; potential consequences for brain and neurocognitive health"],"prefix":"10.1093","volume":"39","author":[{"given":"Dieuwertje E","family":"Kok","sequence":"first","affiliation":[{"name":"Division of Human Nutrition and Health, Wageningen University & Research , P.O. Box 17, 6700 AA Wageningen Stippeneng 4, 6708 WE Wageningen Wageningen Campus l Building 124 (Helix), Wageningen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachael","family":"Saunders","sequence":"additional","affiliation":[{"name":"Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University , Northumberland Building, Newcastle Upon Tyne, NE1 8ST , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Nelson","sequence":"additional","affiliation":[{"name":"Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University , Northumberland Building, Newcastle Upon Tyne, NE1 8ST , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University , Northumberland Building, Newcastle Upon Tyne, NE1 8ST , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianne","family":"Ford","sequence":"additional","affiliation":[{"name":"Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University , Northumberland Building, Newcastle Upon Tyne, NE1 8ST , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C","family":"Mathers","sequence":"additional","affiliation":[{"name":"Human Nutrition & Exercise Research Centre, Centre for Healthier Lives, Population Health Sciences Institute, Newcastle University , Room M2.060, 2nd floor William Leech Building, Framlington Place, Newcastle upon Tyne, NE2 4HH , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill A","family":"McKay","sequence":"additional","affiliation":[{"name":"Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University , Northumberland Building, Newcastle 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