Almeida Mara Ribeiro, Mabasa Lawrence, Crane Courtney, Park Chung S, Venâncio Vinícius Paula, Bianchi Maria Lourdes Pires, Antunes Lusânia Maria Greggi
School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
Department of Animal Sciences, North Dakota State University, Fargo, North Dakota, USA.
Mol Nutr Food Res. 2016 Jul;60(7):1615-24. doi: 10.1002/mnfr.201500950. Epub 2016 Mar 29.
Vitamin B6 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 B6 -deficient or B6 -supplementated diets in the hippocampus of rat dams and their offspring.
Female Wistar rats were fed three different diets: control (6 mg vitamin B6 /kg), supplemented (30 mg vitamin B6 /kg) or deficient diet (0 mg vitamin B6 /kg), from 4 weeks before pregnancy through lactation. Newborn pups (10 days old) from rat dams fed vitamin B6 -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 B6 supplementation or deficiency did not change hippocampal global DNA methylation.
A maternal vitamin B6 -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.
维生素B6在大脑发育中起关键作用，母体缺乏维生素B6会影响后代的γ-氨基丁酸（GABA）能、血清素能、谷氨酸能和多巴胺能系统。然而，这些神经学变化背后的分子机制尚未完全了解。因此，我们旨在评估母体维生素B6缺乏或补充饮食可调节大鼠母鼠及其后代海马体中那些神经递质代谢和信号通路的哪些成分。
雌性Wistar大鼠在怀孕前4周直至哺乳期喂食三种不同的饮食：对照饮食（6毫克维生素B6/千克）、补充饮食（30毫克维生素B6/千克）或缺乏饮食（0毫克维生素B6/千克）。喂食维生素B6缺乏饮食的大鼠母鼠所生的新生幼崽（10日龄）出现高同型半胱氨酸血症，谷氨酸脱羧酶1（Gad1）、成纤维细胞生长因子2（Fgf2）和谷氨酰胺合成酶（Glul）的mRNA水平显著增加，而谷氨酰胺酶（Gls）和色氨酸羟化酶1（Tph1）的mRNA水平下调。维生素B6补充或缺乏并未改变海马体整体DNA甲基化。
母体维生素B6缺乏饮食通过调节Gad1、Glul、Gls和Tph1的mRNA表达影响后代中与GABA、谷氨酸和血清素代谢相关基因的表达。
