Inositol prevents folate-resistant neural tube defects in the mouse.
Clinical trials demonstrate that up to 70% of neural tube defects (NTDs) can be prevented by folic acid supplementation in early pregnancy, whereas the remaining NTDs are resistant to folate. Here, we show that a second vitamin, myo-inositol, is capable of significantly reducing the incidence of spinal NTDs in curly tail mice, a genetic model of folate-resistant NTDs. Inositol increases flux through the inositol/lipid cycle, stimulating protein kinase C activity and upregulating expression of retinoic acid receptor beta, specifically in the caudal portion of the embryonic hindgut. This reduces the delay in closure of the posterior neuropore, the embryonic defect that is known to lead directly to spina bifida in curly tail embryos. Our findings reveal a molecular pathway of NTD prevention and suggest the possible efficacy of combined treatment with folate and inositol in overcoming the majority of human NTDs.
Greene
N D
ND
Neural Development Unit, Institute of Child Health, University of London, UK.
Copp
A J
AJ
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology; D005260:Female; D005492:Folic Acid / Q000494:pharmacology*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D066298:In Vitro Techniques; D007294:Inositol / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008817:Mice, Mutant Strains; D009436:Neural Tube Defects / Q000517:prevention & control*; D011247:Pregnancy; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D018168:Receptors, Retinoic Acid; C082925:retinoic acid receptor beta; D016718:Arachidonic Acid; D007294:Inositol; D005492:Folic Acid; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate