Developmental Exposure to Perchlorate Alters Synaptic Transmission in Hippocampus of the Adult Rat 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] Address correspondence to M.E. Gilbert, Neurotoxicology Division (MD-B105-05) , National Health and Environmental Effects Research Laboratory, 109 TW Alexander Dr., U.S. EPA, Research Triangle Park, NC 27711 USA. Telephone: (919) 541-4394. Fax: (919) 541-4849. E-mail: gilbert.mary@epa.gov Supplemental Material is available online at http://www.ehponline.org/members/2008/11089/suppl.pdf We thank A. Jarabek, K. Crofton, D. Herr, and T. Zoeller for critical reviews of an earlier version of this manuscript ; J. Olin for preparation of histologic material ; K. Das, T. Stoker, and C. Lau for conducting thyroid-stimulating hormone assays ; and W. Anderson, J. Farmer, K. Jarema, R. MacPhail, and P. Phillips for assistance with various phases of this project. This work was supported by a National Research Council Associateship Award to L.S. and by the U.S. Environmental Protection Agency. This document has been subjected to review by the National Health and Environmental Effects Research Laboratory and approved for publication. Approval does not signify that the contents reflect the views of the agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use. The authors declare they have no competing financial interests. Received 19 November 2007 ; accepted 5 March 2008. The full version of this article is available for free in HTML or PDF formats. |