Developmental Exposure to Perchlorate Alters Synaptic Transmission in Hippocampus of the Adult Rat

Abstract

BackgroundPerchlorate 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.ObjectivesThe purpose of this study was to evaluate neurologic function in rats after developmental exposure to perchlorate.MethodsPregnant 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.ResultsAt 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.ConclusionsDose-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.

Developmental Iodine Deficiency and Hypothyroidism Impair Spatial Memory in Adolescent Rat Hippocampus: Involvement of CaMKII, Calmodulin and Calcineurin

“…The period from gestation to adolescence is critical for CNS development and maturation, in which the brain growth and learning ability are vulnerable to exposures to some toxicants and stimulations (Frank et al 2009). In adult rats, it has been shown that thyroid hormones reduction by perchlorate irreversibly impairs synaptic transmission (Gilbert and Sui 2008). In agreement with this observation, we have previously shown that, in adult rats, developmental ID and hypothyroidism impairs LTP in CA1 region (Dong et al 2005).…”

A method for the analysis of six thyroid hormones in thyroid gland by liquid chromatography–tandem mass spectrometry

“…These results support the hypothesis that perchlorate can competitively inhibit iodide uptake by the TG via NIS, and can subsequently reduce the production of THs. Although it has been reported that oral administration of perchlorate to rats via drinking water decreased serum T 4 and T 3 , not only in dams but also in fetuses and neonates [27][28][29]35], the results of our study suggest that, instead, the secretion of active THs into the bloodstream is reduced due to reduced TH production in the TG. Furthermore, our results suggest that adverse effects of perchlorate on TH homeostasis are more pronounced under iodide-deficient conditions.…”

“…In experimental studies using rats, perchlorate exposure decreased serum levels of T 4 and T 3 and increased thyroid stimulating hormone (TSH) levels [27,28]. High doses of perchlorate in rodents during fetal development resulted in permanent detriment to the brain function of the pup [29]. Oral administration of perchlorate to rats via drinking water increased TG weight and induced accompanying histopathological changes in the TG at a dose level of 10 mg/kg/day, but changes were not seen in other tissues and organs; this finding confirmed that the TG is the principal target organ for perchlorate toxicity, in the rat [27].…”

Endocrine disruptors and thyroid hormone physiology

“…Gilbert and Sui [34] recently reported the results of exposing pregnant female rats to perchlorates in drinking water in order to evaluate neurologic development in rat pups after in utero exposure. They found that the highest 11 exposure to perchlorate during development caused a reduction in T4 levels in pups on post-natal day 21.…”