eprintid: 10113241 rev_number: 25 eprint_status: archive userid: 608 dir: disk0/10/11/32/41 datestamp: 2020-10-27 14:05:46 lastmod: 2021-12-07 23:32:40 status_changed: 2020-10-27 14:05:46 type: article metadata_visibility: show creators_name: Harlan De Crescenzo, A creators_name: Panoutsopoulos, AA creators_name: Tat, L creators_name: Schaaf, Z creators_name: Racherla, S creators_name: Henderson, L creators_name: Leung, K-Y creators_name: Greene, NDE creators_name: Green, R creators_name: Zarbalis, KS title: Deficient or Excess Folic Acid Supply During Pregnancy Alter Cortical Neurodevelopment in Mouse Offspring ispublished: pub divisions: UCL divisions: B02 divisions: D13 divisions: G22 keywords: cortical development, folate metabolism, mouse, neurogenesis, projection neurons note: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. abstract: Folate is an essential micronutrient required for both cellular proliferation through de novo nucleotide synthesis and epigenetic regulation of gene expression through methylation. 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. date: 2020-09-30 date_type: published official_url: https://doi.org/10.1093/cercor/bhaa248 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1817042 doi: 10.1093/cercor/bhaa248 pii: 5913010 lyricists_name: Greene, Nicholas lyricists_name: Leung, Kit-Yi lyricists_id: NDEGR34 lyricists_id: KYLEU59 actors_name: Jayawardana, Anusha actors_id: AJAYA51 actors_role: owner full_text_status: public publication: Cerebral Cortex article_number: bhaa248 event_location: United States issn: 1460-2199 citation: Harlan De Crescenzo, A; Panoutsopoulos, AA; Tat, L; Schaaf, Z; Racherla, S; Henderson, L; Leung, K-Y; ... Zarbalis, KS; + view all <#> Harlan De Crescenzo, A; Panoutsopoulos, AA; Tat, L; Schaaf, Z; Racherla, S; Henderson, L; Leung, K-Y; Greene, NDE; Green, R; Zarbalis, KS; - view fewer <#> (2020) Deficient or Excess Folic Acid Supply During Pregnancy Alter Cortical Neurodevelopment in Mouse Offspring. Cerebral Cortex , Article bhaa248. 10.1093/cercor/bhaa248 <https://doi.org/10.1093/cercor%2Fbhaa248>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10113241/1/Greene_bhaa248.pdf