Wang F D, Bian W, Kong L W, Zhao F J, Guo J S, Jing N H
Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai.
Cell Res. 2001 Jun;11(2):135-41. doi: 10.1038/sj.cr.7290078.
Effects of maternal dietary zinc deficiency on prenatal and postnatal brain development were investigated in ICR strain mice. From d 1 of pregnancy (E0) until postnatal d 20 (P20), maternal mice were fed experimental diets that contained 1 mg Zn/kg/day (severe zinc deficient, SZD), 5 mg Zn/kg/day (marginal zinc deficient, MZD), 30 mg Zn/kg/day (zinc adequately supplied, ZA) or 100 mg Zn/kg/day (zinc supplemented, ZS and pair-fed, PF). Brains of offspring from these dietary groups were examined at various developmental stages for expression of nestin, an intermediate filament protein found in neural stem cells and young neurons. Immunocytochemistry showed nestin expression in neural tube 10.5 d post citrus (dpc) as well as in the cerebral cortex and neural tube from 10.5 dpc to postnatal d 10 (P10). Nestin immunoreactivities in both brain and neural tube of those zinc-supplemented control groups (ZA, ZS, PF) were stronger than those in zinc-deficient groups (SZD and MZD). Western blot analysis confirmed that nestin levels in pooled brain extracts from each of the zinc-supplemented groups (ZA, ZS, PF) were much higher than those from the zinc-deficient groups (SZD and MZD) from 10.5 dpc to P10. Immunostaining and Western blots showed no detectable nestin in any of the experimental and control group brains after P20. These observations of an association between maternal zinc deficiency and decreased nestin protein levels in brains of offspring suggest that zinc deficiency suppresses development of neural stem cells, an effect which may lead to neuroanatomical and behavioral abnormalities in adults.
在ICR品系小鼠中研究了母体饮食锌缺乏对产前和产后大脑发育的影响。从妊娠第1天（E0）到出生后第20天（P20），给母鼠喂食含1 mg Zn/kg/天（严重锌缺乏，SZD）、5 mg Zn/kg/天（边缘锌缺乏，MZD）、30 mg Zn/kg/天（锌供应充足，ZA）或100 mg Zn/kg/天（锌补充，ZS和配对喂养，PF）的实验饮食。在不同发育阶段检查这些饮食组后代的大脑中巢蛋白（一种在神经干细胞和年轻神经元中发现的中间丝蛋白）的表达。免疫细胞化学显示，在妊娠10.5天（dpc）的神经管以及从10.5 dpc到出生后第10天（P10）的大脑皮层和神经管中均有巢蛋白表达。那些锌补充对照组（ZA、ZS、PF）的大脑和神经管中的巢蛋白免疫反应性强于锌缺乏组（SZD和MZD）。蛋白质印迹分析证实，从10.5 dpc到P10，每个锌补充组（ZA、ZS、PF）的合并脑提取物中的巢蛋白水平远高于锌缺乏组（SZD和MZD）。免疫染色和蛋白质印迹显示，P20后任何实验组和对照组的大脑中均未检测到巢蛋白。这些关于母体锌缺乏与后代大脑中巢蛋白水平降低之间关联的观察结果表明，锌缺乏会抑制神经干细胞的发育，这种影响可能导致成年期神经解剖学和行为异常。
