Journal
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
Volume 24, Issue 7, Pages 1202-1212Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jnutbio.2012.09.004
Keywords
Diabetes mellitus; Folic acid; Hyperglycemia; Neural progenitors
Funding
- National Basic Research Program of China (973 Program) [2011CB966201]
- National Natural Science Foundation of China [81071057]
- Ministry of Education of China [20110131110036]
- Natural Science Foundation of Shandong Province [2012GSF11842, ZR2010HQ022]
- Shandong University [2012JC006]
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Folic acid has been shown to decrease the incidence of neural tube defects (NTDs) in normal and hyperglycemic conditions, but the influence of folic acid on the development of central nervous system is not fully understood. Here, we aimed to explore the effects of folic acid, especially high dose of folic acid, on the characteristics of neural progenitors in embryos of hyperglycemic and diabetic mouse. Hyperglycemic and diabetic pregnant mice were given 3 mg/kg or 15 mg/kg folic acid from embryonic day 0.5 (E0.5) and were euthanased on E11.5, E13.5 or E18.5. The incidence of NTDs at E13.5 was counted. The proliferation, apoptosis and differentiation of neural progenitors and neuronal migration were determined using BrdU incorporation assay, TUNEL assay, immunofluorescence, Western blot and real-time reverse transcriptase polymerase chain reaction. Both normal and high doses of folic acid decreased the incidence of NTDs, promoted proliferation and reduced apoptosis of neuroepithelial cells in embryos of hyperglycemic and diabetic mice. Importantly, folic acid, especially at high dose, might affect the premature differentiation of neural progenitors in embryos of hyperglycemic and diabetic pregnancy. This may be attributed to changes of messenger RNA expression levels of some basic-helix-loop-helix transcription factors. In addition, folic acid might be involved in regulating neuronal migration in embryos of hyperglycemic and diabetic pregnancy. These findings suggest that periconceptional supplementation of folic acid, especially at high dose, may be a double-edged sword because it may result in undesirable outcomes affecting both the neuronal and glial differentiation in hyperglycemic and diabetic pregnancy. (C) 2013 Elsevier Inc. All rights reserved.
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