Journal
MOLECULAR BRAIN RESEARCH
Volume 134, Issue 2, Pages 309-322Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.molbrainres.2004.11.001
Keywords
choline deficiency; neural precursor cells; gene array; cell proliferation; gene expression; neuronal development
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Funding
- NCI NIH HHS [CA16086] Funding Source: Medline
- NIA NIH HHS [P01 AG009525-160005, AG09525] Funding Source: Medline
- NIDDK NIH HHS [R01 DK055865-07, DK55865, P30 DK056350-08, DK56350] Funding Source: Medline
- NIEHS NIH HHS [ES10126, P30 ES010126-089008, R21 ES012997-03, ES012997] Funding Source: Medline
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Choline is an essential nutrient and an important methyl donor. Choline deficiency alters fetal development of the hippocampus in rodents and these changes are associated with decreased memory function lasting throughout life. Also, choline deficiency alters global and genespecific DNA methylation in several models. This gene expression profiling study describes changes in cortical neural precursor cells from embryonic day 14 mice, after 48 h of exposure to a choline-deficient medium. Using Significance Analysis of Microarrays, we found the expression of 1003 genes to be significantly changed (from a total of 16,000 total genes spotted on the array), with a false discovery rate below 5%. A total of 846 genes were overexpressed while 157 were underexpressed. Classification by gene ontology revealed that 331 of these genes modulate cell proliferation, apoptosis, neuronal and glial differentiation, methyl metabolism, and calcium-binding protein classes. Twenty-seven genes that had changed expression have previously been reported to be regulated by promoter or intron methylation. These findings support our previous work suggesting that choline deficiency decreases the proliferation of neural precursors and possibly increases premature neuronal differentiation and apoptosis. (c) 2004 Elsevier B.V. All rights reserved.
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