Evaluation of the chromosomal instability and mRNA expression of genes related to neurogenesis and neurotransmitter metabolism in the offspring from dams treated with vitamin B6 deficient or supplemented diets

Abstract

Vitamin B6 has a crucial role in the central nervous system formation and its deficiency during pregnancy causes abnormalities in brain development and reduces neurotransmitters such dopamin and gamma-aminobutyric acid (GABA) in the striatum of offspring. However, the molecular mechanisms involved in these processes are not fully understood. Thus, the aim of this study is to investigate the effects of maternal vitamin B6 supplementation and deficiency on the DNA of offspring through the evaluation of chromosomal instability and mRNA expression of genes related to neurogenesis and neurotransmitter metabolism. Female Wistar rats will be treated with 3 different diets: control (6 mg vitamin B6/kg diet); supplemented (30 mg vitamin B6/kg diet) and deficient diet (0 mg vitamin B6/kg diet). The offsprings will be divided into 2 groups: postnatal and adults that will receive control diet and then will be euthanized 10 and 100 days after birth, respectivelly. Dams will be euthanized after the weaning period. The chromosomal intability will be evaluated by comet assay in liver, brain and peripheral blood and by the micronucleus test in bone marrow and peripheral blood. The mRNA expression of neurogenin (Neurog1), neutrin 1 (Ntn1), glutamate decarboxylase 1 (Gad1), 4-aminobutyrate aminotransferase (Abat) and monoamine oxidase A (Maoa) genes will be evaluated in brain by real time PCR. The results of this study will provide further knowledge about the molecular mechanisms of vitamin B6 during embrionic development and thus will supply more evidence about the correct use of this nutrient in diet.