Downregulation of hippocampal NMDA receptor expression by prenatal exposure to dioxin
Nayyar, T.; Wu, J.; Hood, D.B.
Cellular and Molecular Biology 49(8): 1357-1362
2003
ISSN/ISBN: 0145-5680 PMID: 14984010 Document Number: 8739
Gestational exposure to the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) has been implicated as causative to disparities between ethnic groups with respect to learning disabilities. Dioxin is an extremely toxic environmental pollutant that bioaccumulates in maternal adipose tissue, and is transferred to the developing organism during gestation and lactation. Long-term cognitive deficits have been reported following prenatal exposure to dioxin. N-methyl-D-aspartate (NMDA) receptors in the central nervous system (CNS) have been well known to play an important role in the activity-dependent synaptic plasticity underlying learning and memory and in CNS development including brain cell differentiation. Here, the effects of prenatal exposure to dioxin on the developmental expression profiles of rat hippocampal NMDA receptor subtype 1 mRNA and protein was examined. F-344 rats were exposed to 0 and 700 ng of dioxin/kg on gestational day 15. Real-time PCR and Western blot analysis clearly revealed that dioxin significantly downregulated NMDAR1 mRNA and protein expression during the first postnatal month. The study provides support to the hypothesis that NMDA receptors are important targets for dioxin-induced neurotoxicity in F1 preweaning pups. The results also support the concept that prenatal exposure to dioxin may contribute to the pathogenesis of diseases in the adult.
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