铁过量补充导致仔猪海马铁过载并损害社会新颖性识别。

Iron Oversupplementation Causes Hippocampal Iron Overloading and Impairs Social Novelty Recognition in Nursing Piglets.

机构信息

Departments of Nutrition University of California Davis, Davis, CA.

Departments of Animal Science, University of California Davis, Davis, CA.

出版信息

J Nutr. 2019 Mar 1;149(3):398-405. doi: 10.1093/jn/nxy227.

DOI:10.1093/jn/nxy227

PMID:30624730

Abstract

BACKGROUND

Iron oversupplementation in healthy term infants may adversely affect growth and cognitive development.

OBJECTIVE

We hypothesized that early-life iron excess causes systemic and central nervous system iron overload, and compromises social behavior.

METHODS

The nursing pig was used as a translational model in a completely randomized study. On postnatal day (PD) 1, 24 pigs (1.57 ± 0.28 kg mean ± standard deviation body wt) were assigned to the following treatment groups: 1) nonsupplemented iron-deficient group (NON); 2) control group (CON), intramuscularly injected with iron dextran (100 mg Fe) on PD2; 3) moderate iron group (MOD), orally administered ferrous sulfate at 10 mg Fe · kg body wt-1 · d-1; and 4) high iron group (HIG), orally administered ferrous sulfate at 50 mg Fe · kg-1 · d-1. Piglets were nursed by sows during the study from PD1 to PD21. Tissue iron was analyzed by atomic absorption spectrophotometry. Messenger RNA and protein expression of iron regulator and transporters were analyzed by quantitative reverse transcriptase-polymerase chain reaction and Western blot. A sociability test was performed on PD19-20.

RESULTS

Both MOD and HIG treatments (5.51 and 9.85 µmol/g tissue), but not CON (0.54 µmol/g), increased hepatic iron as compared with NON (0.25 µmol/g, P < 0.05). Similarly, the hippocampal iron concentrations in the MOD and HIG groups were 14.9% and 31.8% higher than that of NON, respectively (P < 0.05). In comparison with NON, MOD and HIG treatment repressed DMT1 in duodenal mucosa by 4- and 46-fold, respectively (P < 0.05); HIG drastically induced HAMP in liver by 540-fold (P < 0.05); iron-supplemented groups reduced TFRC in the hippocampus by <1-fold (P < 0.05). However, duodenal expression of ferroportin, the predominant transporter in basal membrane, was not affected by treatment. Despite normal sociability, the MOD and HIG pigs displayed deficits in social novelty recognition (P = 0.004).

CONCLUSIONS

Duodenal ferroportin was hyporesponsive to iron excess (MOD and HIG), which caused hippocampal iron overload and impaired social novelty recognition in nursing pigs.

摘要

背景

健康足月婴儿铁过量补充可能会对生长和认知发育产生不良影响。

目的

我们假设早期铁过量会导致全身和中枢神经系统铁过载，并损害社会行为。

方法

采用完全随机研究，以哺乳仔猪为转化模型。于产后第 1 天（postnatal day，PD）1 时，将 24 头仔猪（1.57±0.28kg 平均±标准差体重）分配至以下处理组：1）未补充铁缺乏组（NON）；2）对照组（CON），PD2 时肌肉内注射铁右旋糖苷（100mgFe）；3）中等铁组（MOD），口服硫酸亚铁 10mgFe·kg-1·d-1；4）高铁组（HIG），口服硫酸亚铁 50mgFe·kg-1·d-1。研究期间，仔猪由母猪哺乳，从 PD1 至 PD21。原子吸收分光光度法分析组织铁。定量逆转录-聚合酶链反应和 Western blot 分析铁调节因子和转运蛋白的信使 RNA 和蛋白表达。于 PD19-20 时进行社交能力测试。

结果

MOD 和 HIG 处理组（5.51 和 9.85µmol/g 组织），而非 NON 处理组（0.25µmol/g，P<0.05），肝铁均增加。同样，MOD 和 HIG 组的海马铁浓度分别比 NON 组高 14.9%和 31.8%（P<0.05）。与 NON 组相比，MOD 和 HIG 处理组分别使十二指肠黏膜 DMT1 抑制 4 倍和 46 倍（P<0.05）；HIG 使肝脏 HAMP 急剧增加 540 倍（P<0.05）；铁补充组使海马 TFRC 减少不到 1 倍（P<0.05）。然而，治疗并未影响基底膜中铁转运蛋白-1 的十二指肠表达。尽管社交能力正常，但 MOD 和 HIG 仔猪在社交新异性识别方面存在缺陷（P=0.004）。