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Deficient or Excess Folic Acid Supply During Pregnancy Alter Cortical Neurodevelopment in Mouse Offspring
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 generatio...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727343/ https://www.ncbi.nlm.nih.gov/pubmed/32995858 http://dx.doi.org/10.1093/cercor/bhaa248 |
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author | Harlan De Crescenzo, Angelo Panoutsopoulos, Alexios A Tat, Lyvin Schaaf, Zachary Racherla, Shailaja Henderson, Lyle Leung, Kit-Yi Greene, Nicholas D E Green, Ralph Zarbalis, Konstantinos S |
author_facet | Harlan De Crescenzo, Angelo Panoutsopoulos, Alexios A Tat, Lyvin Schaaf, Zachary Racherla, Shailaja Henderson, Lyle Leung, Kit-Yi Greene, Nicholas D E Green, Ralph Zarbalis, Konstantinos S |
author_sort | Harlan De Crescenzo, Angelo |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7727343 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-77273432020-12-16 Deficient or Excess Folic Acid Supply During Pregnancy Alter Cortical Neurodevelopment in Mouse Offspring Harlan De Crescenzo, Angelo Panoutsopoulos, Alexios A Tat, Lyvin Schaaf, Zachary Racherla, Shailaja Henderson, Lyle Leung, Kit-Yi Greene, Nicholas D E Green, Ralph Zarbalis, Konstantinos S Cereb Cortex Original Article 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. Oxford University Press 2020-09-30 /pmc/articles/PMC7727343/ /pubmed/32995858 http://dx.doi.org/10.1093/cercor/bhaa248 Text en © The Author(s) 2020. Published by Oxford University Press. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Harlan De Crescenzo, Angelo Panoutsopoulos, Alexios A Tat, Lyvin Schaaf, Zachary Racherla, Shailaja Henderson, Lyle Leung, Kit-Yi Greene, Nicholas D E Green, Ralph Zarbalis, Konstantinos S Deficient or Excess Folic Acid Supply During Pregnancy Alter Cortical Neurodevelopment in Mouse Offspring |
title | Deficient or Excess Folic Acid Supply During Pregnancy Alter Cortical Neurodevelopment in Mouse Offspring |
title_full | Deficient or Excess Folic Acid Supply During Pregnancy Alter Cortical Neurodevelopment in Mouse Offspring |
title_fullStr | Deficient or Excess Folic Acid Supply During Pregnancy Alter Cortical Neurodevelopment in Mouse Offspring |
title_full_unstemmed | Deficient or Excess Folic Acid Supply During Pregnancy Alter Cortical Neurodevelopment in Mouse Offspring |
title_short | Deficient or Excess Folic Acid Supply During Pregnancy Alter Cortical Neurodevelopment in Mouse Offspring |
title_sort | deficient or excess folic acid supply during pregnancy alter cortical neurodevelopment in mouse offspring |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727343/ https://www.ncbi.nlm.nih.gov/pubmed/32995858 http://dx.doi.org/10.1093/cercor/bhaa248 |
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