INOSITOL PREVENTS FOLATE-RESISTANT NEURAL-TUBE DEFECTS IN THE MOUSE

Clinical trials demonstrate that up to 70% of neural tube defects (NTD s) 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 fo late-resistant NTDs. Inositol increases flux through the inositol/lipi d cycle, stimulating protein kinase C activity and upregulating expres sion of retinoic acid receptor beta, specifically in the caudal portio n of the embryonic hindgut. This reduces the delay in closure of the p osterior neuropore, the embryonic defect that is known to lead directl y to spina bifida in curly tail embryos. Our findings reveal a molecul ar pathway of NTD prevention and suggest the possible efficacy of comb ined treatment with folate and inositol in overcoming the majority of human NTDs.