Downregulation of hippocampal NMDA receptor expression by prenatal exposure to dioxin.
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.
Department of Pharmacology & Center in Molecular and Behavioral Neuroscience, Meharry Medical College, Nashville, TN 37208, USA. tnayyar@mmc.edu
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D000818:Animals; D004198:Disease Susceptibility / Q000139:chemically induced; D015536:Down-Regulation / Q000187:drug effects; D004785:Environmental Pollutants / Q000009:adverse effects; D005260:Female; D006624:Hippocampus / Q000737:chemistry / Q000196:embryology / Q000378:metabolism*; D020258:Neurotoxicity Syndromes / Q000209:etiology; D000072317:Polychlorinated Dibenzodioxins / Q000009:adverse effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D016194:Receptors, N-Methyl-D-Aspartate / Q000032:analysis / Q000187:drug effects* / Q000235:genetics
D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate