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Developmental Thyroid Hormone Insufficiency Impairs Visual Contrast Sensitivity in Adult Male Offspring.
GILBERT, M. E., L. Degan, AND W. K. BOYES. Developmental Thyroid Hormone Insufficiency Impairs Visual Contrast Sensitivity in Adult Male Offspring. Presented at Society of Toxicology 49th Annual meeting, Salt Lake City, UT, March 07 - 11, 2010.
The results suggest that modest reductions in thyroid function limited to the perinatal period are sufficient to permanently alter visual system function in adulthood.
Severe thyroid hormone (TH) insufficiency during early development results in alterations in brain structure and function. Many environmental agents produce subtle alterations in TH status, but the dose-response relationships for such effects are unclear. We have previously demonstrated alterations in neurophysiology and learning following graded levels of TH insufficiency in the perinatal period. This study examined the impact of TH insufficiency on the visual system. Pregnant LE rats were given 0,1,2, or 3ppm of the TH synthesis inhibitor propylthiouracil (PTU) through the drinking water from gestation (GD6) through lactation. This dose range produced graded reductions in serum T4 20-50% in dams and pups. No significant changes in serum T3 or body weight were observed in dams or pups. Pups were weaned on PN22 and T4 returned to control levels. At -PN60, electrodes were implanted over the visual cortex. One week later visual evoked potentials (VEPs) were recorded from each rat using modulating visual patterns (0.16 cpd) at 0,8, 12,16,24,32,48,64, and 80% contrast. The YEPamplitude at twice the stimulus rate (F2), expressed as a function ofthe log of the stimulus contrast, was used to generate contrast-gain functions, for which the zero-amplitude intercept is interpreted as contrast threshold. The YEP F2 amplitude was significantly reduced in rats treated with PTU.The slope of contrast-amplitude functions was progressively reduced at each successively higher dose. The results suggest that modest reductions in thyroid function limited to the perinatal period are sufficient to permanently alter visual system function in adulthood. These findings are consistent with visual contrast sensitivity deficits seen in children with congenital hypothyroidism. Notably, deficits in hippocampal synaptic function and learning deficits were observed at similar dose levels, suggesting that modest developmental hypothyroidism leads to global physiological deficits in the CNS. (Does not reflect US EPAPolicy)
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