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Developmental exposure to perchlorate alters synaptic transmission in hippocampus of the adult rat.
Citation:
GILBERT, M. E. AND L. SUI. Developmental exposure to perchlorate alters synaptic transmission in hippocampus of the adult rat. Presented at Society of Toxicolgy, Seattle, WA, March 16 - 20, 2008.
Impact/Purpose:
The present study was designed to evaluate the potential neurological effects of TH reductions induced by developmental exposure to perchlorate.
Description:
The Food Quality Protection Act and Safe Drinking Water Act mandate the EPA to identify potential health risks associated with chemicals that act on the endocrine system. Perchlorate, a contaminant found in food and water supplies throughout the USA, blocks iodine uptake into the thyroid gland and reduces circulating levels of thyroid hormone (TH). The present study was designed to evaluate the potential neurological effects of TH reductions induced by developmental exposure to perchlorate. Pregnant Long-Evans dams were exposed to 0, 30, 300 and 1000ppm perchlorate in the drinking water from gestational day 6 until pups were weaned on postnatal day 30. T4, T3 and TSH were determined in male and female offspring at four ages (PN4, PN14, PN21, PN80-90). Adult male offspring were evaluated on a series of behavioral tasks and electrophysiological measures of synaptic function in the hippocampus. T3 and T4 were reduced in pups on PN21 at the highest dose level. T4 in dams was reduced 12%, 24% and 56% in the 30, 300 and 1000ppm dose groups, respectively. Reductions in T4 were associated with an increase in TSH limited to the high dose group and no changes were seen in serum T3. No effects of perchlorate were detected on behavioral measures of motor activity, spatial learning, or fear conditioning. However, in field potentials recorded from the dentate gyrus, reductions in excitatory postsynaptic potentials (EPSP) and population spike (PS) measures were observed. Significant reductions in baseline synaptic transmission of the PS were detected at all dose levels. Reductions in paired inhibitory synaptic transmission were also evident at 300 and 1000ppm dose levels. These findings indicate an irreversible impairment in synaptic transmission of the hippocampus in response to developmental exposure to perchlorate. Deficits were dose-dependent and detectable with relatively minor perturbations of the thyroid axis.