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