You are here:
GESTATIONAL AND LACTATIONAL EXPOSURE TO PROPYLTHIOURACIL INDUCES HYPOTHYROIDISM AND IMPAIRS SYNAPTIC TRANSMISSION AND PLASTICITY IN AREA CA1 OF HIPPOCAMPUS.
Citation:
Sui, L. AND M. E. Gilbert. GESTATIONAL AND LACTATIONAL EXPOSURE TO PROPYLTHIOURACIL INDUCES HYPOTHYROIDISM AND IMPAIRS SYNAPTIC TRANSMISSION AND PLASTICITY IN AREA CA1 OF HIPPOCAMPUS. Presented at Thyroid Hormone and Brain Development: Translating Molecular Mechanisms to Population Risk, NIEHS, RTP, NC, 9/23-25, 2002.
Description:
Although severe developmental hypothyroidism leads to stunted growth, alterations in hippocampal structure, and impaired performance on a variety of behavioral learning tasks, the impact of milder forms of hypothyroidism has not been adequately assessed. Preliminary reports of altered hippocampal synaptic function have indicted reductions in synaptic plasticity in a postnatal model of hypothyroidism. The present study examined field potentials in area CA1 of hippocampal slices in animals exposed gestationally and lactationally to 0, 3 or 10 ppm propylthiouracil (PTU) in the drinking water from gestational day 6 until postnatal day (PN) 30. Neurophysiological assessments were made at two timepoints, between PN21-PN30 and between PN85-100. Input/output and paired pulse functions were collected to assess the integrity of synaptic transmission. Long-term potentiation (LTP) was induced by theta burst stimulation (25 4-pulse bursts, 100 Hz). Long-term depression (LTD) was induced by 15 min of 1 Hz stimulation. No differences were observed between groups in dam body weight gain throughout pregnancy, or in litter size, pup mortality or pup weight for the first two postnatal wks. Dose-dependent reductions in body weight were evident at weaning with significant pup mortality observed in the high dose group between PN14-PN40. No change in EPSP and population spike (PS) amplitudes were evident in slices prepared from PTU-exposed animals relative to controls in slices from young or adult animals. Deficits in paired pulse facilitation, LTP and LTD of the EPSP slope were seen when animals were tested prior to weaning. No effects were observed in the PS measure. In contrast to the effects observed when testing occurred in the immature organism, slices from adult animals revealed an increase in magnitude of LTP of the PS, but no change in EPSP potentiation. As in the young, paired pulse facilitation of the EPSP was reduced in PTU-treated animals. Behavioral assessments are currently underway. These data indicate that pre- and postnatal exposure to PTU produces persistent alterations in hippocampal synaptic transmission and plasticity and these changes may contribute to learning deficits associated with developmental hypothyroidism. (Does not reflect US EPA policy).