Developmental exposure to Perchlorate alters synaptic transmission in hippocampus of the Adult rat

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Authors: Mary E. Gilbert and Li Sui
Date: June 2008
From: Environmental Health Perspectives(Vol. 116, Issue 6)
Publisher: National Institute of Environmental Health Sciences
Document Type: Report
Length: 8,460 words
Lexile Measure: 1370L

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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 ([T.sub.3]) and thyroxine ([T.sub.4]) were reduced in pups on postnatal day 21. [T.sub.4] 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 augmentaions 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]

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Thyroid hormones play crucial roles in the development and maturation of the central nervous system. Severe reductions during critical periods in the prenatal and early postnatal period produce stunted growth and mental retardation in children (for review, see Anderson et al. 2003; Bernal 2002). However, recent reports indicate that children born to women experiencing modest subclinical perturbations of the thyorid axis during pregnancy have reduced IQ (intelligence quotient) scores and subtle deficits in cognition, memory, and visuospatial ability and higher incidence of attention deficit hyperactivity disorder (ADHD) (Haddow et al. 1999; Zoeller and Rovet 2004). Neuroanatomic alterations have also been demonstrated in animal models of modest thyroid dysfunction in early development (Auso et al. 2004; Goodman and Gilbert 2007; Lavado-Autric et al. 2003). These structural deficits are accompanied by impairments in synaptic transmission, auditory function, behavioral and neurophysiologic assessments of learning and memory, and increased seizure sensitivity (Auso et al. 2004; Gilbert et al. 2006; Gilbert and Sui 2006; Goldey et al. 1995; LavadoAutrec et al. 2003; Sui and Gilbert 2003).

Perchlorate is an environmental contaminant that reduces thyroid hormone (Wolff 1998). Ammonium perchlorate is a salt used primarily in solid rocket fuel and propellants, explosives, pyrotechnics, and blasting formulations. Improper disposal and use result in release of the salt to the environment, where it rapidly dissociates to perchlorate anion. Perchlorate anion has been detected in drink ing water supplies, fruits, vegetables, grain, and...

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Gale Document Number: GALE|A181148441