Maternal dietary choline availability alters mitosis, apoptosis and the localization of TOAD-64 protein in the developing fetal rat septum
Maternal dietary choline availability alters mitosis, apoptosis and the localization of TOAD-64 protein in the developing fetal rat septum
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DOI：
10.1016/s0165-3806(99)00057-7
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发表时间：
1999-06-02
期刊：
影响因子：
--
通讯作者：
Zeisel, SH
中科院分区：
文献类型：
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作者：
Albright, CD;Friedrich, CB;Zeisel, SH
母体饮食胆碱含量的改变会改变后代的大脑生化和海马发育，从而导致后代终生的行为改变。为了更好地了解母体饮食、脑细胞结构和行为之间的关系，我们研究了胆碱含量对胎鼠脑隔膜细胞增殖、凋亡和分化的影响。E12天定时妊娠大鼠饲喂不同水平胆碱的AIN-76日粮6 d。我们发现胆碱缺乏（CD）显著降低了鼻中隔附近的祖神经上皮有丝分裂率。此外，我们发现与对照组相比，CD动物隔膜中凋亡细胞数量增加（每切片3.5 +/- 0.5比1.7 +/- 0.5凋亡细胞，p < 0.05）。然而，CD对灰industrium griiseum （IG）的凋亡没有影响，IG是皮层中隔背侧的区域。使用无偏图像分析方法和单克隆抗体，我们发现在CD动物的背外侧隔膜中TOAD-64 kDa蛋白的表达降低，TOAD-64 kDa蛋白是胎儿发育过程中神经元分化的标志物。CD还降低了靠近中隔的IG和皮质板中TOAD-64 kDa蛋白的表达。这些结果表明，怀孕期间饮食中胆碱的可获得性改变了胎儿脑中隔和海马体区域祖细胞有丝分裂、细胞凋亡和早期神经元分化的时间，这两个大脑区域已知与学习和记忆有关。(C) 1999 Elsevier Science B.V.版权所有
Maternal changes in dietary choline availability alter brain biochemistry and hippocampal development in the offspring resulting in lifelong behavioral changes in the offspring. In order to better understand the relationship between maternal diet, brain cytoarchitecture and behavior, we investigated the effects of choline availability on cell proliferation, apoptosis and differentiation in the fetal rat brain septum. Timed-pregnant rats on day E12 were fed AIN-76 diet with varying levels of dietary choline for 6 days. We found that choline deficiency (CD) significantly decreased the rate of mitosis in the progenitor neuroepithelium adjacent to the septum. In addition, we found an increased number of apoptotic cells in the septum of CD animals compared to controls (3.5 +/- 0.5 vs. 1.7 +/- 0.5 apoptotic cells per section; p < 0.05). However, CD had no effect on apoptosis in the indusium griseum (IG), a region of cortex dorsal to the septum. Using an unbiased image analysis method and a monoclonal antibody we found a decreased expression of the TOAD-64 kDa protein, a marker of commitment to neuronal differentiation during fetal development, in the dorsal lateral septum of CD animals. CD also decreased the expression of TOAD-64 kDa protein in the IG and cortical plate adjacent to the septum. These results show that dietary choline availability during pregnancy alters the timing of mitosis, apoptosis and the early commitment to neuronal differentiation by progenitor cells in regions of the fetal brain septum, as well as hippocampus, two brain regions known to be associated with learning and memory. (C) 1999 Elsevier Science B.V. All rights reserved.