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Brain Sci. 2015, 5(1), 14-31; doi:10.3390/brainsci5010014

Microarray Analysis Reveals Higher Gestational Folic Acid Alters Expression of Genes in the Cerebellum of Mice Offspring—A Pilot Study

1
Developmental Biochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA
2
Developmental Neurobiology, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA
3
Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Susan Shur-Fen Gau and Xiaoming Wang
Received: 26 September 2014 / Revised: 19 December 2014 / Accepted: 15 January 2015 / Published: 26 January 2015
(This article belongs to the Special Issue Autism Spectrum Disorder)
View Full-Text   |   Download PDF [266 KB, uploaded 26 January 2015]   |  

Abstract

Folate is a water-soluble vitamin that is critical for nucleotide synthesis and can modulate methylation of DNA by altering one-carbon metabolism. Previous studies have shown that folate status during pregnancy is associated with various congenital defects including the risk of aberrant neural tube closure. Maternal exposure to a methyl supplemented diet also can alter DNA methylation and gene expression, which may influence the phenotype of offspring. We investigated if higher gestational folic acid (FA) in the diet dysregulates the expression of genes in the cerebellum of offspring in C57BL/6 J mice. One week before gestation and throughout the pregnancy, groups of dams were supplemented with FA either at 2 mg/kg or 20 mg/kg of diet. Microarray analysis was used to investigate the genome wide gene expression profile in the cerebellum from day old pups. Our results revealed that exposure to the higher dose FA diet during gestation dysregulated expression of several genes in the cerebellum of both male and female pups. Several transcription factors, imprinted genes, neuro-developmental genes and genes associated with autism spectrum disorder exhibited altered expression levels. These findings suggest that higher gestational FA potentially dysregulates gene expression in the offspring brain and such changes may adversely alter fetal programming and overall brain development. View Full-Text
Keywords: folic acid; DNA methylation; microarray; autism; gene expression; epigenetics; genomic imprinting; prenatal nutrition; brain folic acid; DNA methylation; microarray; autism; gene expression; epigenetics; genomic imprinting; prenatal nutrition; brain
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MDPI and ACS Style

Barua, S.; Kuizon, S.; Chadman, K.K.; Brown, W.T.; Junaid, M.A. Microarray Analysis Reveals Higher Gestational Folic Acid Alters Expression of Genes in the Cerebellum of Mice Offspring—A Pilot Study. Brain Sci. 2015, 5, 14-31.

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