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

本研究观察了妊娠期接触2，3，7，8-四氯二苯并对二恶英（TCDD）对仔鼠运动发育和学习记忆中起重要作用的钙离子/钙调素依赖性蛋白激酶（CaMKIIα）水平和/或活性的影响。在妊娠第15天，对妊娠大鼠口服TCDD或玉米油。实验结果如下：1）出生后4 ~ 14天，测量大鼠在斜坡上转身的时间，检测大鼠运动发育。TCDD组男女的潜伏期均显著长于对照组。2)在19周龄时，在穿梭箱中的回避行为的表现进行了检查，与对照组相比，TCDD组的逃避率的改善较低。TCDD暴露组大鼠眶皮质和杏仁核磷酸化CaMKIIα明显降低，提示TCDD可能影响神经元的活动。3)每种溶液的平均24小时摄入量，持续5天，出生后（P.D.）24-28和P.D.29-33之间进行了比较暴露和对照组。在P.D.29-33的味精消费量显着降低，赖氨酸消费量较高的女性暴露组比对照组。雌性大鼠杏仁核中CaMKIIα的总量显著增加，提示TCDD可能影响了细胞内Ca^2+和Ca^2+转运信号通路。这些结果表明，TCDD暴露在妊娠期和哺乳期干扰神经元发育的大鼠后代通过大脑边缘系统的功能变化。

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.