Folic Acid Deficiency and Late Gestation Brain Development in Mice

Steven H. Zeisel, MD, Ph.D.
University of North Carolina at Chapel Hill
P30ES19126

Background: Neural tube defects are known to be caused by folic acid deficient diets during the early stages of pregnancy. Women are routinely counseled to take folic acid supplements during the early weeks of their pregnancies. In previous work in laboratory animal studies, these researchers discovered the importance of maternal dietary choline intake late in pregnancy for proper development of the hippocampal region of the brain. Because choline and folate are metabolically interrelated, they speculated that folic acid may also be important at later stages.

Advance: Pregnant mice were given either folate-supplemented, control, or folate-deficient diets from days 11-17 of their 21-day pregnancy. The folate-deficient diets decreased the number of neural progenitor cells undergoing cell division by up to 54% in three regions of the fetal brains. In addition the number of apoptotic cells in the fetal brains was two-times higher in the fetal septum for the folate-deficient mouse pups. Pups from the folate-supplemented group did not differ from the control group.

Implication: These results indicate that progenitor cells in fetal forebrains are sensitive to maternal dietary folate intake during late gestation. Applying these results to human pregnancy suggests that folate availability affects brain development long after neural tube closure, and indicates that it may be very important that women ingest adequate amounts of folic acid throughout pregnancy. This may be especially important in those women with genetic polymorphisms in genes of folate metabolism.

Citation: Craciunescu CN, Brown EC, Mar MH, Albright CD, Nadeau MR, Zeisel SH. Folic acid deficiency during late gestation decreases progenitor cell proliferation and increases apoptosis in fetal mouse brain. J Nutr. 2004 Jan;134(1):162-6.