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

Chronic marginal iron intakes during early development in mice result in persistent changes in dopamine metabolism and myelin composition
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DOI:
10.1093/jn/130.11.2821
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发表时间:
2000-11-01
影响因子:
4.2
通讯作者:
Keen, CL
Keen, CL
中科院分区:
医学2区
文献类型:
--
作者:
Kwik-Uribe, CL;Gietzen, D;Keen, CL

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边缘性铁(Fe)缺乏在世界范围内的儿童中普遍存在,但在早期发育过程中慢性边缘性铁摄入的行为和生化影响还没有得到很好的表征。使用小鼠模型,在我们的实验室以前的工作表明,持续的行为障碍的结果,边缘铁摄入量在早期发展。在本研究中,瑞士韦伯斯特小鼠喂养对照铁饮食(75微克铁/克饮食,n = 13窝)或边缘铁饮食(14微克铁/克饮食,n = 16窝)在妊娠期和出生后第75天(PND)在PND 75被杀死的组织矿物质浓度,多巴胺代谢,髓鞘脂肪酸组成,c-和m-乌头酸酶活性的评估。此外,在一组后代(n = 13窝)中评估了这些结局,该组后代在妊娠期和哺乳期饲喂边际铁饲料,然后从PND 21-75饲喂对照饲料。边缘铁小鼠表现出显着差异,脑铁浓度,多巴胺代谢和髓鞘脂肪酸组成相对于对照组小鼠,但是,没有差异的c-或m-乌头酸酶活性在大脑中被证明。出生后消费的铁充足的饮食之间的边缘铁后代没有完全扭转所有观察到的生化紊乱。这项研究表明,在早期发展过程中,慢性边缘铁摄入量可能会导致脑生化的显着变化。这些生化变化的持久性出生后铁补充表明,他们是一个不可逆的后果发展铁限制。
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 mug Fe/g diet, n = 13 litters) or marginal Fe diet (14 mug 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.