Developmental exposure to perchlorate alters synaptic transmission in hippocampus of the adult rat.
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.


OBJECTIVE
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(3)) and thyroxine (T(4)) were reduced in pups on postnatal day 21. T(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 T(4) were associated with increases in thyroid-stimulating hormone in the high-dose group. No changes were seen in serum T(3). 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.
Neurotoxicology Division, US Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA. gilbert.mary@epa.gov
Mary E
ME
Gilbert
Li
L
Sui
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D008297:Male; D010472:Perchlorates / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D020318:Rats, Long-Evans; D009435:Synaptic Transmission / Q000187:drug effects*; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D010472:Perchlorates; D014284:Triiodothyronine; D013972:Thyrotropin; D013974:Thyroxine; C494474:perchlorate