Dietary Choline Reverses Some, but Not All, Effects of Folate Deficiency on Neurogenesis and Apoptosis in Fetal Mouse Brain

In mice, maternal dietary folate, a cofactor in 1-carbon metabolism, modulates neurogenesis and apoptosis in the fetal brain. Similarly, maternal dietary choline, an important methyl-donor, also influences these processes. Choline and folate are metabolically interrelated, and we determined whether choline supplementation could reverse the effects of folate deficiency on brain development. Timed-pregnant mice were fed control (CT), folate-deficient (FD), or folate-deficient, choline-supplemented (FDCS) AIN-76 diets from d 11 to 17 (E11–17) of pregnancy, and on E17, fetal brains were collected for analysis. Compared with the CT group, the FD group had fewer neural progenitor cells undergoing mitosis in the ventricular zones of the developing mouse brain septum (47%; P < 0.01), hippocampus (29%; P < 0.01), striatum (34%; P < 0.01), and anterior and mid-posterior neocortex (33% in both areas; P < 0.01). In addition, compared with CT, the FD diet almost doubled the rate of apoptosis in the fetal septum and hippocampus (P < 0.01). In the FDCS group, the mitosis rates generally were intermediate between those of the CT and FD groups; mitosis rates in the septum and striatum were significantly greater compared with the FD group and were significantly lower than in the CT group only in the septum and neocortex. In the FDCS group, the hippocampal apoptosis rate was significantly lower than in the FD group (P < 0.01) and was the same as in the CT group. In the septum, the apotosis rate in the FDCS group was intermediate between the CT and FD groups' rates. These results suggest that neural progenitor cells in fetal forebrain are sensitive to maternal dietary folate during late gestation and that choline supplementation can modify some, but not all, of these effects