Excessive folic acid intake combined with undernutrition during gestation alters offspring behavior and brain monoamine profiles
Excessive folic acid intake combined with undernutrition during gestation alters offspring behavior and brain monoamine profiles
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DOI：
10.1111/cga.12472
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发表时间：
2022-05-17
影响因子：
1.3
通讯作者：
Udagawa，Jun
中科院分区：
文献类型：
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作者：
Ono，Tetsuo;Hino，Kodai;Udagawa，Jun
妊娠期间增加膳食叶酸可降低后代神经发育障碍的风险;然而，目前尚不清楚母体过量摄入叶酸是否会损害后代的脑功能。我们研究了在妊娠早期（E5.5-E11.5）营养不良的雄性后代在整个妊娠期摄入过量叶酸是否会改变其行为。将母鼠分为4组：对照组（CON，2 mg叶酸/kg食物）、过量叶酸强化组（FF，10 mg叶酸/kg食物）、营养不良组（UN，从E5.5-E11.5减少40%食物）和过量叶酸强化+营养不良组（UN-FF）。在9周龄时，过量的母体叶酸强化诱导了开放视野中的多动和高架十字迷宫中较低的焦虑样行为。这些行为变化伴随着前额叶皮质（PFC）中多巴胺、杏仁核中去甲肾上腺素和背侧中脑（DM）、PFC和杏仁核中5-羟色胺（5-HT）的减少，其中5-HT神经元从DM投射。此外，典型判别分析，包括PFC中的多巴胺和DOPAC浓度，PFC，杏仁核和脑桥中的去甲肾上腺素浓度，以及杏仁核和DM中的5-HT和5-HIAA浓度，正确分类CON，FF，UN和UN-FF组中73.5%的后代。第一个判别函数主要根据营养状况对组进行分类，而第二个函数主要根据叶酸摄入量对组进行分类。我们的研究表明，母亲营养不良和过量叶酸摄入引起的脑单胺谱的联合转化参与了后代的行为改变。
Dietary folic acid augmentation during gestation reduces neurodevelopmental disorder risk in offspring; however, it is still unclear if excessive maternal folic acid intake can impair brain function in offspring. We examined if excessive folic acid intake throughout gestation altered the behavior of male offspring under poor nutrition during early gestation (E5.5–E11.5). Dams were divided into four groups: control (CON, 2 mg folic acid/kg of food), excessive folic acid fortification (FF, 10 mg folic acid/kg of food), undernutrition (UN, 40% food reduction from E5.5–E11.5), and excessive folic acid fortification plus undernutrition (UN‐FF). Excess maternal folic acid fortification induced hyperactivity in the open‐field and lower anxiety‐like behavior in the elevated plus maze at 9 weeks of age. These behavioral changes were accompanied by reduced dopamine in the prefrontal cortex (PFC), norepinephrine in the amygdala, and 5‐hydroxytryptamine (5‐HT) in the dorsal midbrain (DM), PFC, and amygdala where 5‐HT neurons project from the DM. Furthermore, canonical discriminant analysis, including dopamine and DOPAC concentrations in the PFC, norepinephrine concentrations in the PFC, amygdala, and pons, and 5‐HT and 5‐HIAA concentrations in the amygdala and DM, correctly classified 73.5% of the offspring in CON, FF, UN, and UN‐FF groups. The first discriminant function mainly classified groups based on nutritional status, whereas the second function mainly classified groups based on folic acid intake. Our study suggests that combined transformations of brain monoamine profiles by maternal undernutrition and excess folic acid intake is involved in the behavioral alteration of offsprings.