Altered brain neurotrophins at birth: consequence of imbalance in maternal folic acid and vitamin B₁₂ metabolism

Abstract

Folic acid fortification to pregnant women is suggested to mask vitamin B₁₂ deficiency leading to adverse neurologic consequences. The present study examines the effect of maternal folic acid supplementation at normal and excess levels both in the presence and absence of vitamin B₁₂ on levels and expression of brain neurotrophins in Wistar Albino rats. Pregnant female rats were assigned to six dietary groups with varying levels of folic acid and vitamin B₁₂, that is, (NFB: 2 mg folic acid+B₁₂; NFBD: 2 mg folic acid-B₁₂; EFB: 8 mg folic acid+B₁₂; EFBD: 8 mg folic acid-B₁₂; NFBDO: 2 mg folic acid-B₁₂+DHA and EFBDO: 8 mg folic acid-B₁₂+DHA). On day 20 of gestation pup brain samples were collected to assess protein and mRNA levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). Brain BDNF protein and mRNA levels were reduced (P<0.01 for both) in the EFBD group as compared to control. However, NGF protein levels were reduced (P<0.05) only in the EFBD group in comparison to EFB and control. Maternal supplementation of DHA improved pup brain NGF protein levels only in the NFBDO (P<0.05) and EFBDO (P<0.05) groups compared to NFBD and EFBD respectively. Our results suggest that maternal micronutrients during pregnancy play an important role in regulating protein and mRNA levels of neurotrophins. Maternal DHA supplementation to a micronutrient imbalanced diet could ameliorate the negative effects only for NGF but not for BDNF.