Mary E. Gilbert1,2 and Li Sui1,3
1Neurotoxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA; 2Department of Psychology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA; 3National Research Council, Washington, DC, USA
Abstract
Background: Perchlorate is an environmental contaminant that blocks iodine uptake into the thyroid gland and reduces thyroid hormones. This action of perchlorate raises significant concern over its effects on brain development.
Objectives: The purpose of this study was to evaluate neurologic function in rats after developmental exposure to perchlorate.
Methods: Pregnant rats were exposed to 0, 30, 300, or 1,000 ppm perchlorate in drinking water from gestational day 6 until weaning. Adult male offspring were evaluated on a series of behavioral tasks and neurophysiologic measures of synaptic function in the hippocampus.
Results: At the highest perchlorate dose, triiodothyronine (T3) and thyroxine (T4) were reduced in pups on postnatal day 21. T4 in dams was reduced relative to controls by 16%, 28%, and 60% in the 30-, 300-, and 1,000-ppm dose groups, respectively. Reductions in T4 were associated with increases in thyroid-stimulating hormone in the high-dose group. No changes were seen in serum T3. Perchlorate did not impair motor activity, spatial learning, or fear conditioning. However, significant reductions in baseline synaptic transmission were observed in hippocampal field potentials at all dose levels. Reductions in inhibitory function were evident at 300 and 1,000 ppm, and augmentations in long-term potentiation were observed in the population spike measure at the highest dose.
Conclusions: Dose-dependent deficits in hippocampal synaptic function were detectable with relatively minor perturbations of the thyroid axis, indicative of an irreversible impairment in synaptic transmission in response to developmental exposure to perchlorate.
Key words: brain, cognition, development, hippocampus, iodine, learning and memory, neurotoxicity, perchlorate, thyroid hormone. Environ Health Perspect 116:752–760 (2008) . doi:10.1289/ehp.11089 available via http://dx.doi.org/ [Online 6 March 2008]
Environmental Health Perspectives Volume 116, Number 6, June 2008
