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Thyroid Hormone-Dependent Formation of a Subcortical Band Heterotopia (SBH) in the Neonatal Brain is not Exacerbated Under Conditions of Low Dietary Iron
Spring, S., T. Bastian, G. Anderson, AND M. Gilbert. Thyroid Hormone-Dependent Formation of a Subcortical Band Heterotopia (SBH) in the Neonatal Brain is not Exacerbated Under Conditions of Low Dietary Iron. Presented at Intl. Neurotoxicology Associaiton Meeting, Montreal, QU, CANADA, June 27 - July 01, 2015.
This abstract will be presented at the International Neurotoxicology Association Meeting, Montreal, Quebec, Canada, June 27-July 1-2015
Thyroid hormones (TH) are critical for brain development. Modest TH insufficiency in pregnant rats induced by propylthiouracil (PTU) results in formation of a structural abnormality, a subcortical band heterotopia (SBH), in brains of offspring. PTU reduces TH by inhibiting the synthesis enzyme, thyroperoxidase (TPO). Dietary iron deficiency (FeD) also inhibits TPO and reduces serum TH. This study aimed to determine if FeD alone was sufficient to induce a SBH and if a paired insult (FeD+ PTU) would augment its formation. Pregnant SD rats were administered 0 1 3 or 1Oppm PTU via drinking water starting on gestational day (GD) 6. Dietary FeD was induced in a 2nd set of dams beginning on GD2. A 3rd set received FeD on GD2 plus either 1 or 3ppm PTU on GD6. Serum was taken from pups on postnatal day (PN) 15 and dams on PN21. One pup per litter was sacrificed on PN18, the brain fixed and prepared for immunohistochemical detection of SBH. Dose-dependent reductions in T4 were seen in dams and pups exposed to PTU. FeD reduced pup T4 but not dam T4. Neither did FeD combined with PTU reduce dam T4 any further than PTU alone, in fact T4 levels were higher in FeD+PTU than PTU dams. In contrast, pup T4 was reduced more than dam T4, and FeD alone and in combination with PTU produced more severe T4 reductions than with either treatment alone. Consistent with previous results, SBH size and incidence increased with dose ofPTU. No SBH was detected in the offspring of FeD dams. Counter to our hypothesis, neither was the presence or size ofthe SBH further exacerbated with combined treatments of FeD+PTU. Although limited by sample size, combining FeD with PTU lead to an apparent reduction rather than increase in both SBH incidence and size than that seen with comparable doses of PTU alone. As such, T4 levels in dams appear to be a better predictor of structural insult associated with TH insufficiency than those of pups, findings that are consistent with a prenatal origin of SBH formation. Does not reflect EPA policy.
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
TOXICOLOGY ASSESSMENT DIVISION
ENDOCRINE TOXICOLOGY BRANCH