Folic acid supplementation affects apoptosis and differentiation of embryonic neural stem cells exposed to high glucose.
Folic acid (FA) supplementation has been shown to be extremely effective in reducing the occurrence of neural tube defects (NTDs), one of the most common birth defects associated with diabetic pregnancy. However, the antiteratogenic mechanism of FA in diabetes-induced NTDs is unclear. This study investigated the neuroprotective mechanism of FA in neural stem cells (NSCs) exposed to high glucose in vitro. The undifferentiated or differentiated NSCs were cultured in normal D-glucose concentration (NG) or high D-glucose concentration (HG) with or without FA. FA supplementation significantly decreased apoptosis induced by HG and lowered the expression of p53 in the nucleus of undifferentiated NSCs exposed to HG. Administration of FA in differentiated NSCs did not alter their precocious differentiation induced by HG. The increased mRNA expression levels of the basic helix-loop-helix factors including Neurog1, Neurog2, NeuroD2, Mash1, Id1, Id2, and Hes5 in the presence of HG were not significantly affected by FA. The present results provided a cellular mechanism by which FA supplementation may have a potential role in prevention of NTDs in diabetic pregnancies. On the other hand, FA increased the mRNA expression levels of the above transcription factors and accelerated the differentiation of NSCs in the NG medium, suggesting that it may adversely affect the normal differentiation of NSCs. Therefore, the timing and dose of FA would be critical factors in considering FA supplementation in normal maternal pregnancy.
Key Laboratory of the Ministry of Education for Experimental Teratology, Department of Histology and Embryology, Shandong University School of Medicine, No. 44, Wenhua Xi Road, Jinan, Shandong 250012, PR China.
De-yong
DY
Jia
Hui-juan
HJ
Liu
Fu-wu
FW
Wang
Shang-ming
SM
Liu
Eng-Ang
EA
Ling
Kai
K
Liu
Ai-jun
AJ
Hao
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian; D005492:Folic Acid / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects*; D014803:Vitamin B Complex / Q000494:pharmacology*
D009419:Nerve Tissue Proteins; D014803:Vitamin B Complex; D005492:Folic Acid; D052248:Nitric Oxide Synthase Type I; D005947:Glucose