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HYPOTHYRODISM INDUCED BY EARLY POSTNATAL EXPOSURE TO PROPYLTHIOURACIL IMPAIRS SYNAPTIC TRANSMISSION IN VIVO IN THE HIPPOCAMPUS OF THE ADULT RAT.
Citation:
Gilbert, M. E. AND L. Sui. HYPOTHYRODISM INDUCED BY EARLY POSTNATAL EXPOSURE TO PROPYLTHIOURACIL IMPAIRS SYNAPTIC TRANSMISSION IN VIVO IN THE HIPPOCAMPUS OF THE ADULT RAT. Presented at Thyroid Hormone and Brain Development: Translating Molecular Mechanisms to Population Risk, NIEHS, RTP, NC, 9/23-25/2002.
Description:
Thyroid hormones are essential for maturation and function of the mammalian central nervous system. Severe congenital hypothyroidism results in irreversible structural damage and mental retardation in children. Although a variety of environmental contaminants have been demonstrated to alter circulating levels of thyroid hormones (e.g., polychlorinated biphenyls, brominated flame retardants, drinking water contaminants, pesticides), the neurotoxicological effects associated with such hormone reductions have not been adequately assessed. Thyrotoxins such as propylthiouracil (PTU) have been used pervasively in studies designed to determine the role of thyroid hormone in brain development. Although it is well established that the hippocampus is a brain region impacted by hypothyroidism, functional assessment of the neurophysiological integrity of the hippocampus following such treatment is lacking. Moreover, little information is available on more modest perturbations in thyroid hormones that would mimic those induced by environmental agents. This presentation will focus on recent data from our laboratory characterizing the physiological changes associated with developmental hypothyroidism induced by PTU. Synaptic transmission and plasticity in the dentate gyrus and area CA1 of the hippocampus of adult offspring of pregnant dams treated with PTU are clearly altered and differential effects are evident between these two subregions. Exposure limited to the perinatal period produced alterations in synaptic transmission and plasticity in adulthood despite elimination of the contaminant and a return of thyroid hormones to normal range. Increased understanding of the long term consequences of mild perturbation of thyroid hormones during brain development will aid in assessment of the potential health hazards posed by environmental contaminants that interfere with thyroid hormone function. (This abstract does not necessarily reflect EPA policy)