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This dual requirement places a particular demand on folate availability during pregnancy when both rapid cell generation and programmed differentiation of maternal, extraembryonic, and embryonic\/fetal tissues are required. Accordingly, prenatal neurodevelopment is particularly susceptible to folate deficiency, which can predispose to neural tube defects, or when effective transport into the brain is impaired, cerebral folate deficiency. Consequently, adequate folate consumption, in the form of folic acid (FA) fortification and supplement use, is widely recommended and has led to a substantial increase in the amount of FA intake during pregnancy in some populations. Here, we show that either maternal folate deficiency or FA excess in mice results in disruptions in folate metabolism of the offspring, suggesting diversion of the folate cycle from methylation to DNA synthesis. Paradoxically, either intervention causes comparable neurodevelopmental changes by delaying prenatal cerebral cortical neurogenesis in favor of late-born neurons. These cytoarchitectural and biochemical alterations are accompanied by behavioral abnormalities in FA test groups compared with controls. Our findings point to overlooked potential neurodevelopmental risks associated with excessively high levels of prenatal FA intake.<\/jats:p>","DOI":"10.1093\/cercor\/bhaa248","type":"journal-article","created":{"date-parts":[[2020,8,29]],"date-time":"2020-08-29T11:11:31Z","timestamp":1598699491000},"page":"635-649","source":"Crossref","is-referenced-by-count":75,"title":["Deficient or Excess Folic Acid Supply During Pregnancy Alter Cortical Neurodevelopment in Mouse Offspring"],"prefix":"10.1093","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8456-748X","authenticated-orcid":false,"given":"Angelo","family":"Harlan De Crescenzo","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of California, Davis, CA 95817, USA"},{"name":"Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Northern California, 2425 Stockton Boulevard, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexios A","family":"Panoutsopoulos","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of California, Davis, CA 95817, USA"},{"name":"Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Northern California, 2425 Stockton Boulevard, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2446-2088","authenticated-orcid":false,"given":"Lyvin","family":"Tat","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of California, Davis, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6930-1256","authenticated-orcid":false,"given":"Zachary","family":"Schaaf","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, 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Health, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas D E","family":"Greene","sequence":"additional","affiliation":[{"name":"UCL Great Ormond Street Institute of Child Health, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9935-230X","authenticated-orcid":false,"given":"Ralph","family":"Green","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of California, Davis, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0681-2707","authenticated-orcid":false,"given":"Konstantinos S","family":"Zarbalis","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of California, Davis, CA 95817, USA"},{"name":"Institute for Pediatric Regenerative Medicine, Shriners Hospitals for 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