Prenatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin produces alterations in cortical neuron development and a long-term dysfunction of glutamate transmission in rat cerebral cortex

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is considered one of the most toxic dioxin-like compounds. It is ubiquitous in foodstuffs of animal origin and accumulates in the fatty tissues of animals and humans. Prenatal TCDD exposure has been associated, beside other effects, with persistent impaired cognitive development. In the present study, the effects of maternal exposure to TCDD during pregnancy on cortical neuron development at birth and cortical glutamate transmission in new-born, 14- and 60-day-old rat offspring, were investigated. A single dose (0.7μg/kg) of TCDD dissolved in corn oil was orally administrated to the dams on gestational day 18; controls dams were treated with the vehicle. All the experiments have been performed on the male offspring from vehicle-treated (i.e. control group) and TCDD-treated dams. Primary cultures of cerebral cortical neurons obtained from 1-day-old rats born from mothers exposed to TCDD displayed a reduction in cell viability (MTT assay) and an increase in the number of apoptotic nuclei (nuclear staining with Hoechst 33258) possibly associated with altered dendrite outgrowth (MAP2-immunoreactivity) with respect to control cell cultures. These changes were associated with impairment in cortical glutamate transmission, characterized by a reduction in basal and K(+)-evoked outflow as well as a decrease in (3)H]glutamate uptake. Interestingly, the prenatal TCDD-induced alteration of cortical glutamate signaling is persistent since it was also present in 14- and 60-day-old offspring. Taken together, these results suggest that a single prenatal exposure to TCDD produces alterations in cortical neuron development associated with a long-term dysfunction of glutamate transmission in rat cerebral cortex. The possible relevance of these findings for the understanding of the long-lasting cognitive deficit observed in the offspring from mothers exposed to the toxicant during pregnancy, is discussed.