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

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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.