Department of Nutrition, University of California, Davis, Davis, CA, USA.
Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, USA.
J Nutr. 2021 Jan 4;151(1):235-244. doi: 10.1093/jn/nxaa326.
Both iron deficiency and overload may adversely affect neurodevelopment.
The study assessed how changes in early-life iron status affect iron homeostasis and cytoarchitecture of hippocampal neurons in a piglet model.
On postnatal day (PD) 1, 30 Hampshire × Yorkshire crossbreed piglets (n = 15/sex) were stratified by sex and litter and randomly assigned to experimental groups receiving low (L-Fe), adequate (A-Fe), or high (H-Fe) levels of iron supplement during the pre- (PD1-21) and postweaning periods (PD22-35). Pigs in the L-Fe, A-Fe, and H-Fe groups orally received 0, 1, and 30 mg Fe · kg weight-1 · d-1 preweaning and were fed a diet containing 30, 125, and 1000 mg Fe/kg postweaning, respectively. Heme indexes were analyzed weekly, and gene and protein expressions of iron regulatory proteins in duodenal mucosa, liver, and hippocampus were analyzed through qRT-PCR and western blot, respectively, on PD35. Hippocampal neurons stained using the Golgi-Cox method were traced and their dendritic arbors reconstructed in 3-D using Neurolucida. Dendritic complexity was quantified using Sholl and branch order analyses.
Pigs in the L-Fe group developed iron deficiency anemia (hemoglobin = 8.2 g/dL, hematocrit = 20.1%) on PD35 and became stunted during week 5 with lower final body weight than H-Fe group pigs (6.6 compared with 9.6 kg, P < 0.05). In comparison with A-Fe, H-Fe increased hippocampal ferritin expression by 38% and L-Fe decreased its expression by 52% (P < 0.05), suggesting altered hippocampal iron stores. Pigs in the H-Fe group had greater dendritic complexity in CA1/3 pyramidal neurons than L-Fe group pigs as shown by more dendritic intersections with Sholl rings (P ≤ 0.04) and a greater number of dendrites (P ≤ 0.016).
In piglets, the developing hippocampus is susceptible to perturbations by dietary iron, with deficiency and overload differentially affecting dendritic arborization.
铁缺乏和铁过载均可能对神经发育产生不良影响。
本研究通过猪仔模型评估生命早期铁状态变化如何影响铁稳态和海马神经元的细胞结构。
在出生后第 1 天（PD1），30 头汉普夏×约克夏杂交猪仔（n=15/性别）按性别和窝进行分层，随机分为实验组，在预（PD1-21）和断奶后（PD22-35）期间分别接受低（L-Fe）、中（A-Fe）和高（H-Fe）铁补充剂水平。L-Fe、A-Fe 和 H-Fe 组猪仔经口给予 0、1 和 30mgFe·kg体重-1·d-1，预断奶时分别喂养铁含量为 30、125 和 1000mg/kg 的日粮，断奶后。每周分析血红素指数，分别通过 qRT-PCR 和 Western blot 分析十二指肠黏膜、肝脏和海马铁调节蛋白的基因和蛋白表达，在 PD35 时进行。使用 Golgi-Cox 方法对海马神经元进行染色，使用 Neurolucida 在 3-D 中对其树突进行追踪和重建。使用 Sholl 和分支顺序分析对树突复杂性进行量化。
L-Fe 组猪仔在 PD35 时发生缺铁性贫血（血红蛋白=8.2g/dL，血细胞比容=20.1%），并在第 5 周时生长迟缓，最终体重低于 H-Fe 组猪仔（6.6 比 9.6kg，P<0.05）。与 A-Fe 相比，H-Fe 增加了海马铁蛋白表达 38%，而 L-Fe 减少了 52%（P<0.05），表明海马铁储存发生改变。与 L-Fe 组相比，H-Fe 组 CA1/3 锥体神经元的树突复杂性更大，Sholl 环的树突交叉更多（P≤0.04），树突数量更多（P≤0.016）。
在猪仔中，发育中的海马易受膳食铁的干扰，铁缺乏和铁过载对树突分支的影响不同。
