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小鼠早期发育过程中慢性边缘性铁摄入会导致多巴胺代谢和髓鞘成分持续变化。

Chronic marginal iron intakes during early development in mice result in persistent changes in dopamine metabolism and myelin composition.

作者信息

Kwik-Uribe C L, Gietzen D, German J B, Golub M S, Keen C L

机构信息

Department of Nutrition, University of California, Davis, CA 95616, USA.

出版信息

J Nutr. 2000 Nov;130(11):2821-30. doi: 10.1093/jn/130.11.2821.

DOI:10.1093/jn/130.11.2821
PMID:11053527
Abstract

Marginal iron (Fe) deficiency is prevalent in children worldwide, yet the behavioral and biochemical effects of chronic marginal Fe intakes during early development are not well characterized. Using a murine model, previous work in our laboratory demonstrated persistent behavioral disturbances as a consequence of marginal Fe intakes during early development. In the present study, Swiss-Webster mice fed a control Fe diet (75 microgram Fe/g diet, n = 13 litters) or marginal Fe diet (14 microgram Fe/g diet, n = 16 litters) during gestation and through postnatal day (PND) 75 were killed on PND 75 for assessment of tissue mineral concentrations, dopamine metabolism, myelin fatty acid composition, and c- and m-aconitase activities. In addition, these outcomes were assessed in a group of offspring (n = 13 litters) fed a marginal Fe diet during gestation and lactation and then fed a control diet from PND 21-75. Marginal Fe mice demonstrated significant differences in brain iron concentrations, dopamine metabolism and myelin fatty acid composition relative to control mice; however, no difference in c- or m-aconitase activity was demonstrated in the brain. The postnatal consumption of Fe-adequate diets among marginal Fe offspring did not fully reverse all of the observed biochemical disturbances. This study demonstrates that chronic marginal Fe intakes during early development can result in significant changes in brain biochemistry. The persistence of some of these biochemical changes after postnatal Fe supplementation suggests that they are an irreversible consequence of developmental Fe restriction.

摘要

边缘性铁(Fe)缺乏在全球儿童中普遍存在,然而早期发育期间慢性边缘性铁摄入对行为和生化的影响尚未得到充分表征。利用小鼠模型,我们实验室之前的研究表明,早期发育期间边缘性铁摄入会导致持续的行为障碍。在本研究中,在妊娠期间及出生后第75天(PND 75)给瑞士韦伯斯特小鼠喂食对照铁饮食(75微克铁/克饮食,n = 13窝)或边缘性铁饮食(14微克铁/克饮食,n = 16窝),并在PND 75处死小鼠,以评估组织矿物质浓度、多巴胺代谢、髓磷脂脂肪酸组成以及顺乌头酸酶和间乌头酸酶活性。此外,对一组在妊娠和哺乳期喂食边缘性铁饮食、然后从PND 21至75喂食对照饮食的后代(n = 13窝)进行了这些指标的评估。与对照小鼠相比,边缘性铁小鼠在脑铁浓度、多巴胺代谢和髓磷脂脂肪酸组成方面表现出显著差异;然而,在脑中未发现顺乌头酸酶或间乌头酸酶活性存在差异。边缘性铁后代在出生后摄入充足铁的饮食并不能完全逆转所有观察到的生化紊乱。本研究表明,早期发育期间慢性边缘性铁摄入可导致脑生化发生显著变化。出生后补充铁后,其中一些生化变化仍然存在,这表明它们是发育性铁限制的不可逆后果。

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