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DEVELOPMENTAL HYPOTHYROIDISM IMPAIRS HIPPOCAMPAL LEARNING AND SYNAPTIC TRANSMISSION IN VIVO.
Citation:
Gilbert, M. E. AND L. Sui. DEVELOPMENTAL HYPOTHYROIDISM IMPAIRS HIPPOCAMPAL LEARNING AND SYNAPTIC TRANSMISSION IN VIVO. Presented at Society of Toxicology 42nd Annual Meeting, Salt Lake City, UT, March 9-13, 2003.
Description:
A number of environmental chemicals have been reported to alter thyroid hormone (TH) function. It is well established that severe hypothyroidism during critical periods of brain development leads to alterations in hippocampal structure and learning deficits, yet evaluation of modest perturbations of the thyroid axis coupled with more subtle alterations in brain function has been lacking. The present study examined the effects of developmental hypothyroidism on hippocampal function using behavioral and neurophysiological assessments in the intact animal. Thyroid hormone function was reduced in pregnant dams by propylthiouricil (PTU) via the drinking water (0, 3, 10 ppm) from GD 6 to weaning. This regimen reduced serum TH concentrations on PN14. All animals had returned to a euthyroid state at time of testing. At 5-6 mon of age, spatial learning was assessed in male offspring in a Morris water maze. Between 4-7 mon of age, neurophysiological examination of perforant path-dentate gyrus field potentials was performed in vivo. Input/output (I/O) functions probed the integrity of synaptic transmission. Paired pulses were delivered to examine inhibitory function (PPD) and presynaptic transmission (PPF). Long-term potentiation (LTP) was induced by theta burst stimulation to assess neuroplasticity. PTU induced dose-dependent impairments in spatial learning in the absence of cue learning deficits or reductions in swim speed. Electrophysiologically, population spikes and EPSP slopes were dose-dependently reduced, and LTP was impaired. In contrast, paired pulse tests revealed a shift to more facilitated responses as a function of PTU treatment. These findings corroborate earlier data from our laboratory demonstrating alterations in synaptic function following a higher dose of PTU exposure occurring primarily during lactation and suggest that hippocampal neurophysiological assessments may prove valuable in defining the lower end of the dose-response function for chemicals that alter thyroid function early in development. (Does not reflect US EPA policy).