Maternal vitamin B sub(6) deficient or supplemented diets on expression of genes related to GABAergic, serotonergic, or glutamatergic pathways in hippocampus of rat dams and their offspring

• Published in: Molecular nutrition & food research 2016-07, Vol.60 (7), p.1615-1624
• Main Authors: Almeida, Mara Ribeiro, Mabasa, Lawrence, Crane, Courtney, Park, Chung S, Venancio, Vinicius Paula, Bianchi, Maria Lourdes Pires, Antunes, Lusania Maria Greggi
• Format: Article
• Language: English
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.201500950

Scope Vitamin B sub(6) plays crucial roles on brain development and its maternal deficiency impacts the gamma-aminobutyric acid (GABA)ergic, serotonergic, glutamatergic, and dopaminergic systems in offspring. However, the molecular mechanisms underlying these neurological changes are not well understood. Thus, we aimed at evaluating which components of those neurotransmitter metabolism and signaling pathways can be modulated by maternal vitamin B sub(6)-deficient or B sub(6)-supplementated diets in the hippocampus of rat dams and their offspring. Methods and results Female Wistar rats were fed three different diets: control (6 mg vitamin B sub(6)/kg), supplemented (30 mg vitamin B sub(6)/kg) or deficient diet (0 mg vitamin B sub(6)/kg), from 4 weeks before pregnancy through lactation. Newborn pups (10 days old) from rat dams fed vitamin B sub(6)-deficient diet presented hyperhomocysteinemia and had a significant increase in mRNA levels of glutamate decarboxylase 1 (Gad1), fibroblast growth factor 2 (Fgf2), and glutamate-ammonia ligase (Glul), while glutaminase (Gls) and tryptophan hydroxylase 1 (Tph1) mRNAs were downregulated. Vitamin B sub(6) supplementation or deficiency did not change hippocampal global DNA methylation. Conclusion A maternal vitamin B sub(6)-deficient diet affects the expression of genes related to GABA, glutamate, and serotonin metabolisms in offspring by regulating Gad1, Glul, Gls, and Tph1 mRNA expression. Rat dams were fed with control, vitamin B sub(6)-supplemented or B sub(6)-deficient diets. Newborn pups from rat dams fed B sub(6)-deficient diet presented hyperhomocysteinemia and had increased hippocampal mRNA levels of Gad1 and Glul, while Gls and Tph1 were downregulated. Adult offpspring from rat dams fed supplemented diet showed decreased mRNA levels of Ntn1 in hippocampus. There were no differences on mRNA expression, plasma homocysteine, and global DNA methylation in rat dams.