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Effects of neonatal exposure of 2, 3, 7, 8-TCDD on the neurodevelopment related to brain limbic system of rat off-springs

新生儿暴露2,3,7,8-TCDD对子代大鼠脑边缘系统相关神经发育的影响

基本信息

批准号：
18590577
负责人：
NISHIJO Muneko
金额：
$ 2.36万
依托单位：
Kanazawa Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

The effects of 2, 3, 7, 8- tetrachlorodibenzo-p-dioxin (TCDD) during pregnancy on motor development and the level and/or activity of Ca^<2+>/calmodulin-dependent protein kinase (CaMKIIα), which plays an important role in learning and memory of rat off-springs were investigated in this study. TCDD or corn oil was orally administered to pregnant rats during the 15th day of pregnancy. The following experiments were conducted and obtained the results.1) From the 4th to 14th day after birth, measurement the time of turning around on the slope was performed to test motor development. The latent time of TCDD group was significantly longer than that of controls in both sexes. 2) At the age of the 19th weeks, performance of avoidance behavior in a shuttle box was examined after conditioning with a tone and electric shock.Improvement of escape rates was lower in TCDD group as compared with that of controls in male rats. Phosphorylated CaMKIIα in the orbital cortex and amygdala were significantly decreased in the exposed male group, suggesting that TCDD might affect on neuronal activity. 3) Averaged 24 hours intake of each solution for 5 days, postnatal day (P.D.) 24-28 and P.D.29-33 were compared between exposed and control groups. MSG consumption during P.D.29-33 was significantly lower, and lysine consumption was higher in the female exposed group than those in controls. A total CaMKIIα in the amygdala was significantly increased in the exposed female group, suggesting that TCDD might affect intra-cellular Ca^<2+> and Ca^<2+> transport signaling pathways. These results suggested that TCDD exposure during pregnancy and lactation disturbs neuronal development in rat offspring through functional changes in the limbic system of brain.

本研究探讨了妊娠期间 2,3,7,8-四氯二苯并-对二恶英 (TCDD) 对运动发育以及 Ca^2+/钙调蛋白依赖性蛋白激酶 (CaMKIIα) 水平和/或活性的影响，CaMKIIα 在大鼠后代的学习和记忆中起着重要作用。在怀孕第15天给怀孕大鼠口服TCDD或玉米油。进行了以下实验并获得结果：1)出生后第4天至第14天，测量在斜坡上转身的时间，以测试运动发育。两性中TCDD组的潜伏时间均显着长于对照组。 2)在第19周龄时，在用音调和电击调节后检查在穿梭箱中的回避行为表现。与对照组相比，TCDD组雄性大鼠逃避率的改善较低。在暴露的男性组中，眼眶皮层和杏仁核中的磷酸化 CaMKIIα 显着降低，表明 TCDD 可能会影响神经元活动。 3) 比较暴露组和对照组之间 5 天、产后 (P.D.) 24-28 和 P.D.29-33 各溶液的平均 24 小时摄入量。 P.D.29-33 期间，女性暴露组的味精消耗量显着低于对照组，而赖氨酸消耗量则高于对照组。暴露的女性组杏仁核中总CaMKIIα显着增加，表明TCDD可能影响细胞内Ca^2+和Ca^2+转运信号通路。这些结果表明，妊娠期和哺乳期接触 TCDD 会通过大脑边缘系统的功能变化扰乱大鼠后代的神经元发育。