Maternal Chronic Folate Supplementation Ameliorates Behavior Disorders Induced by Prenatal High‐Fat Diet Through Methylation Alteration of BDNF and Grin2b in Offspring Hippocampus

Scope Maternal consumption of a high‐fat diet (HFD) during pregnancy increases the risk of behavioral problems. Folate plays an important role in neuroplasticity and the preservation of neuronal integrity. This study aims at determining the influence of diets supplemented with folate on offspring behavior, and the mechanisms involved. Methods and results Female mice were fed a control diet, an HFD, control diet supplemented with folate, or an HFD supplemented with folate for 5 weeks before mating. Open field task and elevated plus maze are used to evaluate the offspring behaviors. Results showed that offspring cognitive performance and anxiety‐related behaviors, including those related to open field exploration and elevated plus maze, were significantly improved when dams were treated with folate in pregnancy. Moreover, the maternal folate supplement decreased BDNF and Grin2b methylation and upregulated their expressions in the brain of offspring, which were associated with decreasing the expression of DNA methyltransferases compared with those dams were treated only HFD in pregnancy. Conclusion Maternal folate supplementation ameliorates behavior disorders induced by prenatal high‐fat diet. The beneficial effects were associated with methylation and expression alteration of BDNF and Grin2b genes. The study aims to investigate the effects of maternal folate supplemented on a high‐fat diet (HFD) during pregnancy in offspring. It is found that high‐fat diet supplemented with folate relieves offspring weight, anxiety‐related behaviors and upregulates the expression of neurodevelopmental‐related genes BDNF and Grin2b in the offspring brain comparing to group treated HFD alone. Moreover, the maternal folate supplement decreases BDNF and Grin2b methylation, which suggests that an epigenetic mechanism is involved in the beneficial effects of folate.