Science Inventory

Neurobehavioral Consequences Induced by Developmental iodine deficiency and perchlorate exposure

Citation:

Bell, K., W. Oshiro, Katherine OShaughnessy, J. Ford, AND M. Gilbert. Neurobehavioral Consequences Induced by Developmental iodine deficiency and perchlorate exposure. DNTS Meeting, San Diego, CA, June 23 - 26, 2019.

Impact/Purpose:

Quantitative adverse outcome pathways (qAOPs) are under development for the neurodevelopmental consequences of thyroid disruption. Combined effects of thyroid perturbation from insults from different points along the thyroid axis are described as AOP networks that may improve predictions of adverse health consequences. Thyroid hormones (TH) are critical for brain development and iodine is a critical element for thyroid hormone synthesis. Perchlorate is an environmental contaminant that reduces access of iodine to the thyroid gland and thereby interferes with thyroid hormone synthesis. This work was conducted to ascertain the combined effects iodine deficiency with perchlorate exposure on thyroid-dependent neurodevelopmental consequences at the hormonal, molecular, cell signaling, anatomical and behavioral ends of the AOP continuum. The preliminary findings reported here are on behavioral outcomes in a fear-based context learning paradigm. These data will be used to refine qAOP models.

Description:

Severe iodine deficiency (ID) has long been associated with hypothyroidism and neurological impairments in humans. The environmental contaminant perchlorate also reduces TH production by interfering with iodine uptake into the thyroid gland. Our previous studies independently examined the impact of either dietary ID or drinking water exposure to perchlorate. Although these treatments both reduced serum THs and impaired hippocampal synaptic transmission, no deficits were observed in a hippocampal-dependent task of contextual fear learning. In the present study we hypothesized that an ID diet in conjunction with perchlorate exposure may exacerbate TH insufficiency and result in fear learning deficits. Female rats were maintained on either an iodine controlled or ID diet for a minimum of four weeks before breeding. A subset of each group was administered ammonium perchlorate via the drinking water (0 or 300ppm) beginning on gestational day 6 until weaning on postnatal day (PN) 21 creating 4 treatment conditions. Once dams gave birth, pups were euthanized during the neonatal period to assess serum THs. Trace fear conditioning was later examined in adult male offspring. Results revealed that ID reduced serum T4 by 35% in naive female rats prior to breeding. On PN2, serum T4 in pups born to ID dams decreased by 20%; and by 57% if dams were both ID and treated with perchlorate. Behavioral results of adult male offspring show that both ID and perchlorate exposure during development did not result in a significant learning deficit. Evaluation of serum and brain THs are underway and will provide additional context for interpretation of these preliminary findings. These data suggest that more robust and sensitive behavioral assays may be required to adequately assess the consequences of early thyroid disruption on brain function. Does not reflect EPA policy.

Record Details:

Record Type:DOCUMENT( PRESENTATION/ POSTER)
Product Published Date:06/26/2019
Record Last Revised:08/02/2019
OMB Category:Other
Record ID: 345885