Conclusion
The results indicate that maternal folic acid supplementation promotes hippocampal neurogenesis and improves learning and memory behavior in mouse offspring. The mechanisms involve modification of DNA methylation on GR alternate promoters and GR upregulation in the hippocampus, which is associated with activation of BDNF/AKT/ERK1/2 signaling.
Results
Adult male mice derived from dams fed basal or folic-acid-supplemented diet (5 mg folic acid/kg) throughout gestation and lactation are used in this study. Maternal folic acid significantly enhances offspring learning and memory with less fear-related behavior. Concurrently, hippocampal neurogenesis is improved with upregulation of brain-derived neurotrophic factor and its downstream AKT/ERK1/2 signaling pathway. More GR immune-positive cells are observed in hippocampus of folic acid group, which are in line with higher GR protein and mRNA abundances. Differential expression of GR exon 1 transcript variants is detected, which is inversely associated with modified DNA methylation on their alternate promoters.