Citation:

Gilbert, M., J. Hedge, L. Valentin-Blasini, B. Blount, K. Kannan, Joe Tietge, R. Zoeller, K. Crofton, J. Jarrett, AND J. Fisher. An animal model of marginal iodine deficiency during development: The thyroid axis and neurodevelopmental outcome. Presented at Society of Toxicology meeting, March 10 - 14, 2013.

Impact/Purpose:

This abstract will be presented at the Society of Toxicology meeting, March 10-14, 2013, San Antonio, TX

Description:

Thyroid hormones (TH) are essential for brain development and iodine is required for TH synthesis. Environmental chemicals that perturb the thyroid axis result in modest reductions in TH, yet there is a paucity of data on the neurological impairments associated with low level TH disruption. This study examined the dose-response characteristics of marginal iodine deficiency (ID) on parameters of thyroid function and neurodevelopment. ID diets were prepared by adding varying concentrations of iodine to a casein-based diet producing 5 nominal iodine levels ranging from ample (1000 jig iodine/kg chow) to deficient (25 jig iodine/kg chow). Female Long Evans rats were maintained on these diets beginning 7 wk prior to breeding until the end of lactation. Dams were sacrificed on gestational days 16 and 20, or when pups were weaned on postnatal day (PN)2 I. Fetal tissue was harvested with sacrifice of the dams, pups were sacrificed on PN 14 and PN2 1. Blood, thyroid gland, and brain were analyzed for iodine, TH, TH precursors and metabolites. Serum and thyroid gland iodine and TH were reduced in the two most deficient diets. T4 was reduced in the fetal brain but was not altered in the neonate. Cognitive function, assessed by acoustic startle, water maze learning and fear conditioning, was unchanged in adult offspring, but excitatory synaptic transmission was impaired in the dentate gyrus by the two most deficient diets. A 15% reduction in cortical T4 in the fetal brain was sufficient to induce permanent reductions in synaptic function in the adult. These findings further suggest that standard behavioral assays do not readily detect neurotoxicity induced by modest developmental TH disruption. (Does not reflect EPA or CDC policy).

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