You are here:
MATERNAL HYPOTHYROXENEMIA LEADS TO PERSISTENT DEFICITS IN HIPPOCAMPAL SYNAPTIC TRANSMISSION AND LEARNING IN OFFSPRING.
Citation:
Sui, L. AND M. E. Gilbert. MATERNAL HYPOTHYROXENEMIA LEADS TO PERSISTENT DEFICITS IN HIPPOCAMPAL SYNAPTIC TRANSMISSION AND LEARNING IN OFFSPRING. Presented at Society for Neuroscience, New Orleans, LA, 11/8-13/2003.
Description:
MATERNAL HYPOTHYROXINEMIA LEADS TO PERSISTENT DEFICITS IN HIPPOCAMPAL SYNAPTIC TRANSMISSION AND LEARNING IN RAT OFFSPRING. M.E. Gilbert1 and Li Sui2, Neurotoxicology Division, 1US EPA and 2National Research Council, Research Triangle Pk, NC 27711.
While severe hypothyroidism during development can cause hippocampal damage and learning deficits, evaluation of modest perturbations of the thyroid axis 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 hormones (TH) were reduced in pregnant LE rats by propylthiouricil (PTU) administered via the drinking water (0, 3, 10 ppm) from GD 6 to weaning of the offspring. This regimen reduced maternal serum T4, increased TSH and had no effect on T3 (hypothyroxinemia). Both T3 and T4 were reduced in the offspring at weaning but returned to control levels at the time of testing. At 5-6 months of age, spatial learning was assessed in a Morris water maze. Between 4-7 months neurophysiological examination of perforant path-dentate gyrus field potentials was performed in vivo. PTU induced dose-dependent deficits in spatial learning without cue learning deficits or reductions in swim speed. Electrophysiologically, population spikes (PS) and EPSP slopes were reduced in a dose-dependent manner. In contrast, paired pulse tests of the PS revealed a shift to more facilitated responses as a function of PTU treatment. Impairment of EPSP slope LTP was coupled with an enhancement of PS LTP. Correlational analyses between behavioral and synaptic indices of hippocampal function are underway. These findings corroborate an earlier demonstration of perturbations in dentate gyrus function with a higher dose of PTU exposure restricted to the postnatal period (Gilbert and Paczkowski, under review), and suggest that even modest hormone insufficiency can lead to permanent impairments in hippocampal function that may contribute to cognitive deficits (Funded by USEPA, does not reflect US EPA policy).