Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, China.
QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
J Nutr. 2019 Dec 1;149(12):2247-2254. doi: 10.1093/jn/nxz168.
Brain iron deposition is a feature of Alzheimer disease and may contribute to its development. However, the relative contribution of dietary iron remains unclear.
We investigated the impact of high dietary iron on brain pathological changes and cognitive function in adult wild-type (WT) mice and amyloid precursor protein/presenilin 1 (APP/PS1) double transgenic mice.
Male WT mice and APP/PS1 mice aged 10 wk were fed either a control diet (66 mg Fe/kg) (WT-Ctrl and APP/PS1-Ctrl) or a high iron diet (14 g Fe/kg) (WT-High Fe and APP/PS1-High Fe) for 20 wk. Iron concentrations in brain regions were measured by atomic absorption spectrophotometry. Brain iron staining and amyloid-β (Aβ) immunostaining were performed. Protein expressions in the hippocampus were determined by immunoblotting. Superoxide dismutase (SOD) activity and malondialdehyde concentration were examined. Cognitive functions were tested with the Morris water maze system.
In the hippocampus, APP/PS1-High Fe mice had significantly higher iron concentration (2.5-fold) and ferritin (2.0-fold) than APP/PS1-Ctrl mice (P < 0.001), and WT-High Fe mice had significantly higher ferritin (2.0-fold) than WT-Ctrl mice (P < 0.001). Interestingly, APP/PS1 mice had significantly higher iron concentration (2-3-fold) and ferritin (2-2.5-fold) than WT mice fed either diet (P < 0.001). Histological analysis indicated that iron accumulated in the hippocampal dentate gyrus region in APP/PS1 mice, consistent with the pattern of Aβ deposition. For both mouse strains, iron treatment induced Aβ and phospho-τ expression (1.5-3-fold) in the hippocampus, but had little impact on oxidative stress and cognitive function. Furthermore, APP/PS1 mice had significantly lower SOD activity and higher malondialdehyde concentration than WT mice in the hippocampus (P < 0.0001), paralleled by apparent cognitive dysfunction.
Dietary iron overload induces iron disorder and Aβ and phospho-τ expression in the hippocampus of adult WT and APP/PS1 transgenic mice.
脑铁沉积是阿尔茨海默病的一个特征，可能对其发展有贡献。然而，膳食铁的相对贡献仍不清楚。
我们研究了高膳食铁对成年野生型（WT）小鼠和淀粉样前体蛋白/早老素 1（APP/PS1）双转基因小鼠脑病理变化和认知功能的影响。
10 周龄雄性 WT 小鼠和 APP/PS1 小鼠分别喂食对照饮食（66mg Fe/kg）（WT-Ctrl 和 APP/PS1-Ctrl）或高铁饮食（14g Fe/kg）（WT-High Fe 和 APP/PS1-High Fe）20 周。原子吸收分光光度法测定脑区铁浓度。进行脑铁染色和淀粉样β（Aβ）免疫染色。免疫印迹法测定海马区蛋白表达。检测超氧化物歧化酶（SOD）活性和丙二醛浓度。用 Morris 水迷宫系统测试认知功能。
在海马区，APP/PS1-High Fe 小鼠的铁浓度（2.5 倍）和铁蛋白（2.0 倍）明显高于 APP/PS1-Ctrl 小鼠（P<0.001），WT-High Fe 小鼠的铁蛋白（2.0 倍）明显高于 WT-Ctrl 小鼠（P<0.001）。有趣的是，APP/PS1 小鼠无论喂食哪种饮食，其铁浓度（2-3 倍）和铁蛋白（2-2.5 倍）均明显高于 WT 小鼠（P<0.001）。组织学分析表明，铁在 APP/PS1 小鼠的海马齿状回区蓄积，与 Aβ沉积的模式一致。两种小鼠品系中铁处理均诱导海马 Aβ和磷酸化τ表达（1.5-3 倍），但对氧化应激和认知功能影响不大。此外，APP/PS1 小鼠的海马 SOD 活性明显低于 WT 小鼠，丙二醛浓度明显高于 WT 小鼠（P<0.0001），同时伴有明显的认知功能障碍。
膳食铁过载诱导成年 WT 和 APP/PS1 转基因小鼠海马铁紊乱、Aβ和磷酸化τ表达。
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